Amyloidosis - Knowledge

715: 742: 727: 821: 790: 766: 802: 778: 754: 593:. Most amyloid-forming proteins are relatively small, but otherwise there is currently no evidence of structural or functional similarities among proteins known to form disease-associated amyloids. One third of amyloid disease is hereditary, in which case there is normally an early age of onset. Half of amyloid-related diseases are sporadic and have a late age of onset – in these cases, the protein aggregation may be associated with aging-related decline in protein regulation. Some medical treatments are associated with amyloid disease, but this is rare. 1854:

of adverse events versus placebo. There is no evidence of an effect on mortality rate. A review of early data from use of patisiran in people with variant cardiac ATTR suggests that it may reduce mortality and hospitalization, however this is still being investigated and requires further investigation. In 2018, patisiran was not recommended by NICE in the UK for hereditary transthyretin-related amyloidosis. As of July 2019 further review however is occurring. It was approved for this use in the United States, however.

283: 693:, memory B cells producing aberrant immunoglobulins or portions of immunoglobulins. Immunofixation electrophoresis of urine or serum is positive in 90% of people with AL amyloidosis. Immunofixation electrophoresis is more sensitive than regular electrophoresis but may not be available in all centers. Alternatively immunohistochemical staining of a bone marrow biopsy looking for dominant plasma cells can be sought in people with a high clinical suspicion for AL amyloidosis but negative electrophoresis. 371:, the heart shows a restrictive filling pattern, with normal to mildly reduced systolic function. AA amyloidosis usually spares the heart. Cardiac amyloidosis can present with symptoms of heart failure including shortness of breath, fatigue, and edema. As cardiac amyloidosis progresses, the amyloid deposition can affect the heart's ability to pump and fill blood as well as its ability to maintain normal rhythm, which leads to worsening heart function and decline in people's quality of life. 34: 1935:. AA amyloidosis is caused by an increase in extracellular deposition of serum amyloid A (SAA) protein. SAA protein levels can rise in both direct and indirect manners, through infection, inflammation, and malignancies. The most common causes of AA amyloidosis in the West are rheumatoid arthritis, inflammatory bowel disease, psoriasis, and 660:, which means a negative result does not exclude the diagnosis of amyloidosis. However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can also be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people. 3805: 1853:

functions similarly to inotersen. Moderate-certainty evidence suggests that patisiran mitigates worsening of peripheral neuropathy and disability from disease progression. Additionally, low-certainty evidence suggests that patisiran mitigates decreases in quality-of-life and slightly reduces the rate

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Historical classification systems were based on clinical factors. Until the early 1970s, the idea of a single amyloid substance predominated. Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. Most classification systems

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but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety. Amyloidosis of the central nervous system can have more severe and systemic presentations that may include life-threatening arrhythmias, cardiac failure, malnutrition, infection, or

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Inotersen blocks gene expression of both wild-type and mutant TTR, reducing amyloid precursor. Moderate-certainty evidence suggests that it mitigates worsening of peripheral neuropathy. Long-term efficacy and safety of inotersen use in people with mutant TTR-related amyloidosis is still be evaluated

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Accumulation of amyloid proteins in the gastrointestinal system may be caused by a wide range of amyloid disorders and have different presentations depending on the degree of organ involvement. Potential symptoms include weight loss, diarrhea, abdominal pain, heartburn (gastrointestinal reflux), and

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Prognosis varies with the type of amyloidosis and the affected organ system. Prognosis for untreated AL cardiac amyloidosis is poor, with a median survival of six months. More specifically, AL amyloidosis can be classified as stage I, II or III based on cardiac biomarkers like Nt-proBNP and cardiac

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transplantation has shown promise in early studies and is recommended for stage I and II AL amyloidosis. However, only 20–25% of people are eligible for stem cell transplant. Chemotherapy treatment including cyclophosphamide-bortezomib-dexamethasone is currently the recommended treatment option for

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Amyloid proteins deposit most commonly inside the knee, followed by hands, wrists, elbow, hip, and ankle, causing joint pain. In males with advanced age (>80 years), there is significant risk of wild-type transthyretin amyloid deposition in synovial tissue of knee joint, but predominantly in old

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Based on available research, liver transplant remains the most effective treatment option for advanced ATTR amyloidosis, protein stabilizing drugs may slow disease progression but were insufficient to justify delay of liver transplant, and newer agents such as patisiran require additional studies.

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Treatment is geared towards decreasing the amount of the involved protein. This may sometimes be achieved by determining and treating the underlying cause. AL amyloidosis occurs in about 3–13 per million people per year and AA amyloidosis in about two per million people per year. The usual age of

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inotersen, the former having recently received FDA approval. Research into treatments for ATTR amyloidosis have compared liver transplantation, oral drugs that stabilize the misfolding protein (including tafamidis and diflunisal), and newer therapeutic agents still being investigated (including

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The modern era of amyloidosis classification began in the late 1960s with the development of methods to make amyloid fibrils soluble. These methods permitted scientists to study the chemical properties of amyloids. Descriptive terms such as primary amyloidosis, secondary amyloidosis, and others

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Neuropathic presentation can depend on the etiology of amyloidosis. People with amyloidosis may experience dysfunction in various organ systems depending on the location and extent of nervous system involvement. For example, peripheral neuropathy can cause erectile dysfunction, incontinence and

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ATTR is now considered to be the most common form of amyloidosis. It may be either age related in wild-type ATTR (ATTRv) or familial transthyretin-associated amyloidosis, is suspected in people with family history of idiopathic neuropathies or heart failure who lack evidence of plasma cell

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People with amyloidosis may have central nervous system involvement, along with peripheral involvement which causes sensory and autonomic neuropathies. Sensory neuropathy develops in a symmetrical pattern and progresses in a distal to proximal manner. Autonomic neuropathy can present as

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People with ATTR, mutant ATTR and wild-type ATTR have a better prognosis when compared to people with AL and may survive for over a decade. Survival time is not associated with gender or age, however, some measures of reduced heart function are associated with a shorter survival time.

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in a phase-III clinical trial as of 2021. Both diflunisal and inotersen may also mitigate declines in quality-of-life, though the evidence for this effect is unclear. For people with cardiac ATTR the effect of inotersen use is inconclusive and requires further investigation. In 2018,

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forms. Both the oligomers and amyloid fibrils can be toxic to cells and can interfere with proper organ function. The relative significance of different aggregation species may depend on the protein involved and the organ system affected.

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was approved by the European Medicines Agency to treat polyneuropathy in adults with hereditary transthyretin amyloidosis. It has since been approved for use in Canada, the European Union and in the USA.

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All amyloid fibril proteins start with the letter "A" followed by the protein suffix (and any applicable specification). See below for a list of amyloid fibril proteins which have been found in humans:

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People affected by amyloidosis are supported by organizations, including the Amyloidosis Research Consortium, Amyloidosis Foundation, Amyloidosis Support Groups, and Australian Amyloidosis Network.

604:-resistant, meaning it can not be degraded or broken down. As a result, amyloid deposits into the body's extracellular space. The process of forming amyloid fibrils is thought to have intermediate 398:

GI bleeding. Amyloidosis may also affect accessory digestive organs including the liver, and may present with jaundice, fatty stool, anorexia, fluid buildup in the abdomen, and spleen enlargement.

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troponin. Survival diminishes with increasing stage, but recent advancements in treatments have improved median survival rates for stages I, II, and III, to 91.2, 60, and 7 months respectively.

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The modern classification of amyloid disease tends to use an abbreviation of the protein that makes the majority of deposits, prefixed with the letter A. For example, amyloidosis caused by

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or light chain determination); binding of particular antibodies to the amyloid found in the tissue (immunohistochemistry); or extraction of the protein and identification of its individual

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Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS. Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat. J Biol Chem 1985; 260 (21) 11793-11798

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People undergoing long-term hemodialysis (14–15 years) can develop amyloidosis from accumulation of light chains of the HLA 1 complex which is normally filtered out by the kidneys.

535:, a susceptibility to bleeding with bruising around the eyes, termed "raccoon-eyes". Amyloid purpura is caused by amyloid deposition in the blood vessels and reduced activity of 3802:"Alnylam Announces FDA Approval of Amvuttra (vutrisiran), an RNAi Therapeutic for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults" 714: 286:

Skin features of amyloidosis cutis dyschromica. Hyperpigmented and hypopigmented macules on (A) lower legs, (B) back and waist, (C) waist. (D) Individual blisters on upper arm.

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AL has the highest incidence at approximately 12 cases per million persons per year and an estimated prevalence of 30,000 to 45,000 cases in the US and European Union.

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Lin HM, Gao X, Cooke CE, Berg D, Labotka R, Faller DV, et al. (June 2017). "Disease burden of systemic light-chain amyloidosis: a systematic literature review".

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Amyloidosis has a combined estimated prevalence of 30 per 100,000 persons with the three most common forms being AL, ATTR, and AA. The median age at diagnosis is 64.

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Diagnosis of amyloidosis generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various

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ter Haar NM, Oswald M, Jeyaratnam J, Anton J, Barron KS, Brogan PA, et al. (September 2015). "Recommendations for the management of autoinflammatory diseases".

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Pettersson-Kastberg J, Aits S, Gustafsson L, Mossberg A, Storm P, Trulsson M, et al. (November 2008). "Can misfolded proteins be beneficial? The HAMLET case".

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Diflunisal binds to misfolded mutant TTR protein to prevent its buildup, like how tafamidis works. Low-certainty evidence indicates that it mitigates worsening of

4190:"Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study" 3865: 708:

AA is suspected on clinical grounds in individuals with longstanding infections or inflammatory diseases. AA can be identified by immunohistochemistry staining.

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Outcomes in a person with AA amyloidosis depend on the underlying disease, organ(s) affected, and correlate with the concentration of serum amyloid A protein.

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is called amyloidoma. It is commonly found in cervical, lumbar, and sacral vertebrae. Those affected may be presented with bone pain due to bone lysis, lumbar

457:. Adrenal infiltration may be harder to appreciate given that its symptoms of orthostatic hypotension and low blood sodium concentration may be attributed to 1811:, a low toxicity oral agent that prevents destabilization of correctly folded protein. Studies showed tafamidis reduced mortality and hospitalization due to 741: 4188:

Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-Enari S, Paetau A, Tienari PJ, Myllykangas L (1 January 2008).

433:(fingerlike projections that increase the intestinal area available for absorption of food), begin to erode the functionality of the villi, presenting a 3835: 1864:

gene-editing technique, several participants had an "80% to 96% drop in TTR levels, on par or better than the average of 81%" who were given patisiran.

4356: 2382: 472:, although it is not known if this is functionally important. The major component of pancreatic amyloid is a 37-amino acid residue peptide known as 290:

The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. The kidney and heart are the most common organs involved.

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Amyloidosis symptoms are often vague and require different physician specialists for diagnosis. Telltale symptoms may include an enlarged tongue (

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Magrinelli F, Fabrizi GM, Santoro L, Manganelli F, Zanette G, Cavallaro T, Tamburin S, et al. (Cochrane Neuromuscular Group) (April 2020).

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in knee, hip, shoulder and interphalangeal joints. Amyloid light chains deposition in shoulder joint causes enlarged shoulders, also known as "

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is termed "ATTR". Deposition patterns vary between people but are almost always composed of just one amyloidogenic protein. Deposition can be

726: 4233: 2172: 563:, and altered taste. Tongue enlargement does not occur in ATTR or AA amyloidosis. Deposition of amyloid in the throat can cause hoarseness. 4697: 834: 1945:

Wild-type transthyretin (ATTR) amyloidosis is found in a quarter of elderly at postmortem. ATTR is found in 13–19% of people experiencing

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Chiti F, Dobson CM (June 2017). "Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade".

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Secondary (reactive) amyloidoses occur as a complication of some other chronic inflammatory or tissue-destroying disease. Examples are

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constipation, pupillary dysfunction, and sensory loss depending on the distribution of amyloidosis along different peripheral nerves.

160:, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, 3985:"Prognostic impact of light-chain and transthyretin-related categories in cardiac amyloidosis: A systematic review and meta-analysis" 2726:

Takahashi N, Glockner J, Howe BM, Hartman RP, Kawashima A (May 2016). "Taxonomy and Imaging Manifestations of Systemic Amyloidosis".

219:, and three proteins can identify as either. These proteins can become irregular due to genetic effects, as well as through acquired 860:

to chronic inflammatory conditions). Some classification systems included myeloma-associated, familial, and localized amyloidosis.

801: 4071: 3035: 3334:"Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee" 1874:(FDA) in June 2022, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. 789: 765: 270:

onset of these two types is 55 to 60 years old. Without treatment, life expectancy is between six months and four years. In the

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Other forms are due to different diseases causing overabundant or abnormal protein production – such as with overproduction of

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A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is

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In AA, symptoms may improve if the underlying condition is treated. In people who have inflammation caused by AA amyloidosis,

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Coles LS, Young RD (May 2012). "Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension".

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Nguyen TX, Naqvi A, Thompson TL, Wilson RH (Spring 2018). "Musculoskeletal Manifestations of Amyloidosis: A Focused Review".

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The type of the amyloid protein can be determined in various ways: the detection of abnormal proteins in the bloodstream (on

4682: 3653: 3525:"Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence-Based Recommendations" 864:(e.g., senile amyloidosis), which are not based on cause, provide little useful information and are no longer recommended. 429:

and 2.4% of AA amyloidosis. One suggested mechanism for the observed malabsorption is that amyloid deposits in the tips of

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About 60 amyloid proteins have been identified so far. Of those, at least 36 have been associated with a human disease.

678:. Immunohistochemistry can identify AA amyloidosis the majority of the time, but can miss many cases of AL amyloidosis. 3857: 1703: 2221:

Gertz MA, Dispenzieri A (July 2020). "Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review".

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Amyloid deposits in tissue can cause enlargement of structures. Twenty percent of people with AL amyloidosis have an

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Management of ATTR amyloidosis will depend on its classification as wild type or variant. Both may be treated with

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Feeling tired, weight loss, swelling of the legs, shortness of breath, bleeding, feeling light headed with standing

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Additionally, based on the tissues in which it is deposited, it is divided into mesenchymal (organs derived from

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AL was previously considered the most common form of amyloidosis, and a diagnosis often begins with a search for

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Kyriakou P, Mouselimis D, Tsarouchas A, Rigopoulos A, Bakogiannis C, Noutsias M, Vassilikos V (December 2018).

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AA amyloidoses is the most common form in developing countries and can complicate longstanding infections with

504:. Aβ2MG amyloidosis (Hemodialysis associated amyloidosis) tends to deposit in synovial tissue, causing chronic 3827: 274:

about one per 1,000 deaths are from systemic amyloidosis. Amyloidosis has been described since at least 1639.

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Mok KH, Pettersson J, Orrenius S, Svanborg C (March 2007). "HAMLET, protein folding, and tumor cell death".

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Merlini G, Dispenzieri A, Sanchorawala V, Schönland SO, Palladini G, Hawkins PN, Gertz MA (October 2018).

2763:"Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis" 2374: 856:) amyloidosis, in which no associated clinical condition was identified, and secondary amyloidosis (i.e., 649: 489:

age deposition of wild type transthyretin is seen in cardiac ventricles. ATTR deposits have been found in

4743: 4738: 4722: 4349:"Press Announcements - FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease" 2069: 1695: 887: 653: 652:, known as a "fat pad biopsy", due to its ease of acquisition. An abdominal fat biopsy is not completely 3680:"Patisiran for treating hereditary transthyretin-related amyloidosis [ID1279] | Guidance | NICE" 4766: 4646: 4381:

Cristóbal Gutiérrez H, Pelayo-Negro AL, Gómez Gómez D, Martín Vega MÁ, Valero Domínguez M (July 2020).

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Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJ, Sekijima Y, et al. (December 2020).

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space. Of the 37 proteins so far identified as being vulnerable to amyloid formation, only four are

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The roles of inotersen and patisiran in cardiac ATTR amyloidosis are still being investigated.

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Systemic amyloidoses affect more than one body organ or system. Examples are AL, AA and Aβ2m.

690: 329:. Approximately 20% and 40–60% of people with AL and AA amyloidosis respectively progress to 201: 193: 115: 3572: 4866: 4612: 4561: 4067: 1785: 1675:

An older clinical method of classification refers to amyloidoses as systemic or localised:

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Marques N, Azevedo O, Almeida AR, Bento D, Cruz I, Correia E, et al. (October 2020).

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are used for an average duration of 20 months. If TNF-alpha inhibitors are not effective,

667:. In amyloidoma, there will be low T1 signal with gadolinium injection and low T2 signal. 581:

diseases. The vast majority of proteins that have been found to form amyloid deposits are

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Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, et al. (August 2021).

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with preserved ejection fraction, making it a very common form of systemic amyloidosis.

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Senile systemic amyloidosis was determined to be the primary cause of death for 70% of

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Treatment depends on the type of amyloidosis that is present. Treatment with high dose

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stain may be used. A number of imaging techniques such as a Nuclear Medicine PYP scan,

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Ando Y, Coelho T, Berk JL, Cruz MW, Ericzon BG, Ikeda S, et al. (February 2013).

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to look for specific known mutations in transthyretin that predispose to amyloidosis.

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is rare, occurring in 5% of people. Splenic dysfunction, leading to the presence of

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Kaku M, Berk JL (October 2019). "Neuropathy Associated with Systemic Amyloidosis".

2582: 2572: 2522: 2474: 2341: 2331: 2282: 2230: 2138: 2084: 1962: 1902: 1718: 876: 872: 582: 430: 402: 325:. Several types of amyloidosis, including the AL and AA types, are associated with 266:. Due to the variable presentation, a diagnosis can often take some time to reach. 216: 161: 4157: 4140: 4109: 3904: 3604:"Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis" 3350: 3333: 3096: 2513:

Ebert EC, Nagar M (March 2008). "Gastrointestinal manifestations of amyloidosis".

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In the amyloid deposition of the joints, there will be a decreased signal in both

4841: 4819: 4789: 4602: 4495: 4398: 875:(affecting many different organ systems) or organ-specific. Many amyloidoses are 838: 702: 532: 490: 434: 334: 271: 189: 157: 111: 107: 4045: 2478: 701:

which separates mutated forms of transthyretin. Findings can be corroborated by

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can be infiltrated. It is estimated that 10–20% of people with amyloidosis have

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Buxbaum JN (July 2018). "Oligonucleotide Drugs for Transthyretin Amyloidosis".

4272: 4257:"Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021" 3957: 3940: 3267: 1932: 903: 891: 807: 686:

is the most reliable method of identifying the different forms of amyloidosis.

523:, and a variety of neurological symptoms. Vertebral fractures are also common. 454: 426: 368: 314: 310: 259: 228: 224: 4541: 4205: 4001: 3984: 3722: 3302: 3112: 2739: 2577: 2088: 1682:

Localised amyloidoses affect only one body organ or tissue type. Examples are

857: 409:, two biomarkers of liver injury, which is seen in about one third of people. 401:

Accumulation of amyloid proteins in the liver can lead to elevations in serum

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changes may be present, showing low voltage and conduction abnormalities like

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Eldhagen P, Berg S, Lund LH, Sörensson P, Suhr OB, Westermark P (June 2021).

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Falk RH, Comenzo RL, Skinner M (September 1997). "The systemic amyloidoses".

2411:. In Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J (eds.). 1992: 1946: 1928: 1812: 1801: 1773: 1008: 1003: 868: 586: 543:, two clotting proteins that lose their function after binding with amyloid. 450: 446: 422: 352: 263: 97: 4469: 4189: 3540: 3157:

Wechalekar AD, Gillmore JD, Hawkins PN (June 2016). "Systemic amyloidosis".

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Amyloid-forming proteins aggregate into distinctive fibrillar forms with a

552: 414: 410: 255: 173: 42: 3770: 3753: 2486: 2320:"Guideline of transthyretin-related hereditary amyloidosis for clinicians" 585:, so the misfolding and formation of amyloid occurs outside cells, in the 207:

There are about 36 different types of amyloidosis, each due to a specific

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and is co secreted with insulin." (Rang and Dale's Pharmacology, 2015.)

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The deposition of amyloid proteins in the bone marrow without causing

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Amyloid deposition in the heart can cause both diastolic and systolic

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In beta 2-microglobulin amyloidosis, males have high risk of getting

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arise from a disease with disordered immune cell function, such as

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or 'amylin.' This is stored with insulin in secretory granules in

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National Institute of Diabetes and Digestive and Kidney Diseases

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Metabolic disease involving abnormal deposited amyloid proteins

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Brunger AF, Nienhuis HL, Bijzet J, Hazenberg BP (March 2020).

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Hematology. American Society of Hematology. Education Program

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Falk RH, Alexander KM, Liao R, Dorbala S (September 2016).

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Hoy SM (October 2018). "Patisiran: First Global Approval".

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Xin Y, Hu W, Chen X, Hu J, Sun Y, Zhao Y (November 2019).

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Small bowel duodenum with amyloid deposition Congo red 10X

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on blood smear, occurs in 24% of people with amyloidosis.

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National Institute for Health and Care Excellence (Nice)

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was the only effective treatment. New therapies include

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people with AL Amyloidosis not eligible for transplant.

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showing amyloid deposition (red fluffy material) in the

392: 317:. This can lead to high levels of protein in the urine ( 2921:"Amyloidosis: pathogenesis and new therapeutic options" 2171:. Genetic and Rare Diseases Information Center (GARD). 621:. The most useful stain in the diagnosis of amyloid is 4346: 2671: 3751: 1015:

Heart mainly in males, lung, ligaments, tenosynovium

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Skin conditions resulting from errors in metabolism

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Biochemical and Biophysical Research Communications

629:, makes the amyloid proteins appear apple-green on 4070:. Science. 26 September 2008. pp. 1764–1765. 3466: 3464: 3462: 3198: 3196: 3152: 3150: 2918: 2464: 2317: 1804:inhibitors (e.g., tocilizumab) may be considered. 260:problems are found with multiple peripheral nerves 4254: 3387:Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). 3097:"Systemic immunoglobulin light chain amyloidosis" 2721: 2719: 2672:Rowe K, Pankow J, Nehme F, Salyers W (May 2017). 262:and it is unclear why. Diagnosis is confirmed by 4858: 3202: 2554: 2552: 2381:. U.S. Department of Health and Human Services. 2220: 1710:Another classification is primary or secondary. 747:Small bowel duodenum with amyloid deposition 20X 211:. Within these 36 proteins, 19 are grouped into 4141:"Causes of AA amyloidosis: a systematic review" 4095: 3832:NORD (National Organization for Rare Disorders) 3518: 3516: 3459: 3193: 3147: 3090: 3088: 3086: 2914: 2912: 2910: 1081:terminal variants), skin (C terminal variants) 2824: 2822: 2820: 2818: 2816: 2814: 2716: 4569: 3945:Journal of the American College of Cardiology 3010:Journal of the American Society of Nephrology 2999: 2997: 2967: 2864: 2862: 2860: 2858: 2856: 2854: 2852: 2549: 2508: 2506: 2504: 2502: 2500: 2498: 2496: 2460: 2458: 2456: 2454: 2264: 2262: 2260: 2216: 2214: 2212: 2210: 1774:tumour necrosis factor (TNF)-alpha inhibitors 1079:Heart, liver, kidney, PNS, testis, larynx (C 600:structure. The beta-sheet form of amyloid is 4068:"Searching for the Secrets of the Super Old" 3934: 3932: 3513: 3381: 3379: 3377: 3282: 3247: 3083: 2907: 2667: 2665: 2663: 2619: 2617: 2615: 2452: 2450: 2448: 2446: 2444: 2442: 2440: 2438: 2436: 2434: 2406: 2402: 2400: 2208: 2206: 2204: 2202: 2200: 2198: 2196: 2194: 2192: 2190: 1815:. Previously, for variant ATTR amyloidosis, 4091: 4089: 3982: 3978: 3976: 3477:The Cochrane Database of Systematic Reviews 3049:Sachchithanantham S, Wechalekar AD (2013). 2919:Merlini G, Seldin DC, Gertz MA (May 2011). 2868: 2811: 4576: 4562: 4031: 3601: 2994: 2849: 2512: 2493: 2413:Harrison's Principles of Internal Medicine 2257: 2077:Rheumatic Disease Clinics of North America 2063: 2061: 2059: 2057: 2022:. Amyloidosis Support Groups. 1 March 2022 1652:EGF-containing fibulin-like extracellular 1584:Odontogenic ameloblast-associated protein 135:3–13 per million per year (AL amyloidosis) 4406: 4280: 4156: 4000: 3956: 3929: 3912: 3769: 3629: 3619: 3548: 3529:Journal of the American Heart Association 3496: 3434: 3374: 3349: 3230: 3220: 3066: 3021: 2944: 2890: 2794: 2699: 2689: 2660: 2612: 2586: 2576: 2431: 2397: 2345: 2335: 2286: 2187: 2124: 2122: 2120: 2118: 2116: 2114: 2067: 2055: 2053: 2051: 2049: 2047: 2045: 2043: 2041: 2039: 2037: 1838:and disability from disease progression. 1468:Pituitary prolactinomas, aging pituitary 697:dyscrasias. ATTR can be identified using 483: 152:is a group of diseases in which abnormal 4086: 3973: 3203:Rosenzweig M, Landau H (November 2011). 2831:Journal of Surgical Orthopaedic Advances 2623: 2515:The American Journal of Gastroenterology 894:), or with continuous overproduction of 281: 4303: 3886: 3006:"Amyloidosis-associated kidney disease" 2369: 2367: 2365: 2311: 1860:In 2021, in a clinical trial using the 493:of patients that underwent surgery for 4859: 3003: 2268: 2111: 2034: 1740:) or parenchymal (organs derived from 4744:ACys+ABri/Cerebral amyloid angiopathy 4698:ATTR/Transthyretin-related hereditary 4557: 4387:European Journal of Hospital Pharmacy 4359:from the original on 7 September 2018 4255:Hasib Sidiqi M, Gertz MA (May 2021). 3038:from the original on 5 December 2011. 2883:10.1146/annurev-biochem-061516-045115 2419:from the original on 29 November 2021 2385:from the original on 19 November 2021 2128: 393:Gastrointestinal and accessory organs 277: 4098:Current Medical Research and Opinion 3608:Drug Design, Development and Therapy 3209:Journal of Hematology & Oncology 2362: 2143:10.1146/annurev.med.57.121304.131243 1519:Cornified epithelia, hair follicles 1017:PNS, ANS, heart, eye, leptomeninges 143:1 per 1,000 people (developed world) 110:, directed at the underlying cause, 4306:The New England Journal of Medicine 3758:The New England Journal of Medicine 3708: 3583:from the original on 8 October 2020 2728:Radiologic Clinics of North America 2467:The New England Journal of Medicine 771:Amyloidosis, blood vessels, H&E 506:inflammation of the synovial tissue 13: 3868:from the original on 15 March 2016 3838:from the original on 16 March 2016 2375:"Amyloidosis & Kidney Disease" 2175:from the original on 24 April 2017 2070:"Amyloidosis: a clinical overview" 1704:medullary carcinoma of the thyroid 1434:Islets of Langerhans, insulinomas 1375:CJD, GSS syndrome, fatal insomnia 795:Amyloidosis, lymph node, polarizer 14: 4888: 4427: 4236:from the original on 14 June 2022 4074:from the original on 9 March 2013 3808:from the original on 14 June 2022 3690:from the original on 20 July 2019 3135:from the original on 14 June 2022 3051:"Imaging in systemic amyloidosis" 2324:Orphanet Journal of Rare Diseases 1877: 846: 374: 3660:from the original on 4 July 2019 3602:Mathew V, Wang AK (6 May 2019). 3415:Annals of the Rheumatic Diseases 2527:10.1111/j.1572-0241.2007.01669.x 2129:Pepys MB (2006). "Amyloidosis". 1293:Aβ protein precursor, wild type 819: 800: 788: 783:Amyloidosis, lymph node, H&E 776: 764: 752: 740: 725: 713: 250:Diagnosis may be suspected when 239:M), and hereditary and old age ( 32: 4767:AApoA1+AFib+ALys/Familial renal 4693:AA/Familial Mediterranean fever 4583: 4340: 4297: 4248: 4181: 4132: 4060: 4025: 3880: 3850: 3820: 3745: 3702: 3672: 3646: 3595: 3565: 3427:10.1136/annrheumdis-2015-207546 3406: 3325: 3101:Nature Reviews. Disease Primers 3042: 2961: 2754: 2603: 1912: 1730:secondary cutaneous amyloidosis 1721:or other immunocyte dyscrasias. 1658:Portal veins, Aging associated 1201:Leukocyte chemotactic factor-2 1150:Apolipoprotein C III, variants 1116:Apolipoprotein A IV, wild type 566: 464:"Amyloid deposits occur in the 245:wild-type transthyretin amyloid 45:) or bruising around the eyes ( 3989:Hellenic Journal of Cardiology 3489:10.1002/14651858.CD012395.pub2 2968:Gertz MA, Rajkumar SV (2010). 2157: 2005: 1670: 1295:Aβ protein precursor, variant 1133:Apolipoprotein C II, variants 577:Amyloidoses can be considered 546: 1: 4813:ACal/Medullary thyroid cancer 4785:Primary cutaneous amyloidosis 4683:Aβ2M/Haemodialysis-associated 4158:10.1080/13506129.2019.1693359 4110:10.1080/03007995.2017.1297930 3905:10.1182/asheducation-2017.1.1 3351:10.1080/13506129.2020.1835263 3171:10.1016/S0140-6736(15)01274-X 2871:Annual Review of Biochemistry 2407:Lewis JB, Neilson EG (2018). 1998: 1726:reactive systemic amyloidosis 665:T1 and T2 weighted MRI images 252:protein is found in the urine 4399:10.1136/ejhpharm-2018-001823 4347:Office of the Commissioner. 2925:Journal of Clinical Oncology 2767:Journal of Internal Medicine 2565:BMC Cardiovascular Disorders 2415:(20 ed.). McGraw Hill. 1957:Treatments for ATTR-related 1937:familial Mediterranean fever 1885: 1872:Food and Drug Administration 1751: 1485:Iatrogenic, local injection 1119:Kidney medulla and systemic 759:Amyloidosis, Node, Congo Red 612: 7: 4739:Familial amyloid neuropathy 4046:10.1016/j.ypmed.2012.03.003 3887:Merlini G (December 2017). 3004:Dember LM (December 2006). 2479:10.1056/NEJM199709253371306 1981: 1952: 1696:isolated atrial amyloidosis 944:All organs, usually except 888:immunoglobulin light chains 178:feeling faint with standing 10: 4893: 4273:10.1038/s41408-021-00483-7 3958:10.1016/j.jacc.2016.06.053 3816:– via Business Wire. 3577:Europeans Medicines Agency 3391:. Philadelphia: Saunders. 3268:10.1016/j.bbrc.2006.12.167 1654:matrix protein 1 (EFEMP1) 1448:Atrial natriuretic factor 1431:Islet amyloid polypeptide 962:Immunoglobulin heavy chain 940:Immunoglobulin light chain 928:Systemic and/or localized 883:in the precursor protein. 650:subcutaneous abdominal fat 570: 344: 293: 4798: 4775: 4757: 4729: 4715: 4708:Organ-limited amyloidosis 4706: 4665: 4591: 4516: 4446: 4206:10.1080/07853890701842988 4002:10.1016/j.hjc.2019.01.015 3862:rarediseases.info.nih.gov 3804:. Alnylam. 13 June 2022. 3723:10.1007/s40265-018-0983-6 3303:10.1080/07853890802502614 3113:10.1038/s41572-018-0034-3 2740:10.1016/j.rcl.2015.12.012 2578:10.1186/s12872-018-0952-8 2169:rarediseases.info.nih.gov 2131:Annual Review of Medicine 2089:10.1016/j.rdc.2013.02.012 2068:Hazenberg BP (May 2013). 1870:was approved by the U.S. 1692:Atrial natriuretic factor 1364:Prion protein, wild type 474:islet amyloid polypeptide 440: 139: 131: 121: 103: 91: 83: 75: 65: 53: 40: 31: 26: 3055:British Medical Bulletin 2972:. Totowa, N.J.: Humana. 2937:10.1200/JCO.2010.32.2271 1499:Lung surfactant protein 852:included primary (i.e., 734:dystrophic calcification 468:of people who also have 413:is common. In contrast, 340: 331:end-stage kidney disease 3541:10.1161/JAHA.120.016614 3389:Robbins Basic Pathology 2013:"Amyloidosis Awareness" 1408:C-cell thyroid tumours 1366:Prion protein variants 1218:Fibrinogen a, variants 1050:Musculoskeletal system 931:Acquired or hereditary 672:protein electrophoresis 625:, which, combined with 557:obstructive sleep apnea 526: 382:orthostatic hypotension 127:Improved with treatment 4749:Aβ/Alzheimer's disease 3222:10.1186/1756-8722-4-47 3023:10.1681/ASN.2006050460 2638:10.1055/s-0039-1688994 2337:10.1186/1750-1172-8-31 2235:10.1001/jama.2020.5493 1369:Prion protein variant 983:(Apo) serum amyloid A 531:A rare development is 517:plasma cell dyscrasias 502:carpal tunnel syndrome 495:lumbar spinal stenosis 484:Musculoskeletal system 361:atrioventricular block 307:glomerular capillaries 287: 198:small fiber neuropathy 186:carpal tunnel syndrome 3771:10.1056/NEJMoa2107454 2626:Seminars in Neurology 2409:"Glomerular Diseases" 1967:small interfering RNA 1961:include TTR-specific 1836:peripheral neuropathy 1536:Senile aortic, media 1235:Cystatin C, variants 691:plasma cell dyscrasia 680:Laser microdissection 561:difficulty swallowing 285: 221:environmental factors 202:autonomic dysfunction 194:biceps tendon rupture 116:organ transplantation 4723:AANF/Isolated atrial 4666:Systemic amyloidosis 4318:10.1056/nejme1805499 4261:Blood Cancer Journal 3621:10.2147/DDDT.S162913 3165:(10038): 2641–2654. 1587:Odontogenic tumours 1373:CJD, fatal insomnia 1170:Kidney, PNS, cornea 900:chronic inflammation 896:acute phase proteins 699:isoelectric focusing 459:autonomic neuropathy 407:alkaline phosphatase 215:, 14 are grouped as 4034:Preventive Medicine 2691:10.7759/cureus.1228 1974:patisiran). 1764:agent, followed by 1715:Primary amyloidoses 1604:Vesicula seminalis 1553:Cornea, hereditary 1184:Lysozyme, variants 1167:Gelsolin, variants 1097:Apolipoprotein A II 902:(which can lead to 835:cardiac amyloidosis 808:Cardiac amyloidosis 555:, that can lead to 461:and heart failure. 425:is seen in 8.5% of 419:Howell-Jolly bodies 347:Cardiac amyloidosis 170:shortness of breath 87:Genetic or acquired 4517:External resources 4194:Annals of Medicine 3291:Annals of Medicine 3068:10.1093/bmb/ldt021 2779:10.1111/joim.13222 2275:Acta Haematologica 2269:Picken MM (2020). 1788:inhibitors (e.g., 1638:Tumour associated 1221:Kidney, primarily 1204:Kidney, primarily 1074:Apolipoprotein A I 986:All organs except 966:All organs except 922:Precursor protein 656:and may result in 579:protein misfolding 415:spleen enlargement 327:nephrotic syndrome 323:nephrotic syndrome 305:often involve the 301:deposition in the 288: 278:Signs and symptoms 209:protein misfolding 4854: 4853: 4850: 4849: 4825:APro/Prolactinoma 4688:AGel/Finnish type 4551: 4550: 3951:(12): 1323–1341. 3717:(15): 1625–1631. 3398:978-1-4160-2973-1 3016:(12): 3458–3471. 2979:978-1-60761-631-3 2931:(14): 1924–1933. 2288:10.1159/000506696 1988:Peptide synthesis 1668: 1667: 1550:Kerato-epithelin 1274:ADanPP, variants 1255:ABriPP, variants 684:mass spectrometry 645:are also in use. 583:secreted proteins 510:shoulder pad sign 491:ligamentum flavum 470:diabetes mellitus 411:Liver enlargement 403:aminotransferases 311:mesangial regions 256:organ enlargement 147: 146: 93:Diagnostic method 60:Internal medicine 21:Medical condition 4884: 4837:AIAPP/Insulinoma 4713: 4712: 4596:forming proteins 4578: 4571: 4564: 4555: 4554: 4444: 4443: 4421: 4420: 4410: 4378: 4369: 4368: 4366: 4364: 4344: 4338: 4337: 4301: 4295: 4294: 4284: 4252: 4246: 4245: 4243: 4241: 4185: 4179: 4178: 4160: 4136: 4130: 4129: 4104:(6): 1017–1031. 4093: 4084: 4083: 4081: 4079: 4064: 4058: 4057: 4040:(Suppl): S9-11. 4029: 4023: 4022: 4004: 3980: 3971: 3970: 3960: 3936: 3927: 3926: 3916: 3884: 3878: 3877: 3875: 3873: 3854: 3848: 3847: 3845: 3843: 3824: 3818: 3817: 3815: 3813: 3798: 3792: 3791: 3773: 3749: 3743: 3742: 3706: 3700: 3699: 3697: 3695: 3676: 3670: 3669: 3667: 3665: 3650: 3644: 3643: 3633: 3623: 3599: 3593: 3592: 3590: 3588: 3569: 3563: 3562: 3552: 3520: 3511: 3510: 3500: 3468: 3457: 3456: 3438: 3421:(9): 1636–1644. 3410: 3404: 3402: 3383: 3372: 3371: 3353: 3329: 3323: 3322: 3286: 3280: 3279: 3251: 3245: 3244: 3234: 3224: 3200: 3191: 3190: 3154: 3145: 3144: 3142: 3140: 3092: 3081: 3080: 3070: 3046: 3040: 3039: 3025: 3001: 2992: 2991: 2965: 2959: 2958: 2948: 2916: 2905: 2904: 2894: 2866: 2847: 2846: 2826: 2809: 2808: 2798: 2758: 2752: 2751: 2723: 2714: 2713: 2703: 2693: 2669: 2658: 2657: 2621: 2610: 2607: 2601: 2600: 2590: 2580: 2556: 2547: 2546: 2510: 2491: 2490: 2462: 2429: 2428: 2426: 2424: 2404: 2395: 2394: 2392: 2390: 2371: 2360: 2359: 2349: 2339: 2315: 2309: 2308: 2290: 2266: 2255: 2254: 2218: 2185: 2184: 2182: 2180: 2165:"AL amyloidosis" 2161: 2155: 2154: 2126: 2109: 2108: 2074: 2065: 2032: 2031: 2029: 2027: 2020:amyloidaware.com 2017: 2009: 1963:oligonucleotides 1817:liver transplant 1719:multiple myeloma 1405:(Pro)calcitonin 1044:β2-microglobulin 1039:β2-microglobulin 916: 915: 823: 804: 792: 780: 768: 756: 744: 729: 717: 431:intestinal villi 369:echocardiography 367:dysfunction. On 233:dialysis-related 227:, inflammation ( 225:light chain (AL) 162:peripheral edema 36: 24: 23: 4892: 4891: 4887: 4886: 4885: 4883: 4882: 4881: 4872:Protein folding 4857: 4856: 4855: 4846: 4842:Type 2 diabetes 4794: 4790:Amyloid purpura 4771: 4753: 4725: 4702: 4661: 4587: 4582: 4552: 4547: 4546: 4512: 4511: 4455: 4430: 4425: 4424: 4379: 4372: 4362: 4360: 4345: 4341: 4302: 4298: 4253: 4249: 4239: 4237: 4186: 4182: 4137: 4133: 4094: 4087: 4077: 4075: 4066: 4065: 4061: 4030: 4026: 3981: 3974: 3937: 3930: 3885: 3881: 3871: 3869: 3856: 3855: 3851: 3841: 3839: 3826: 3825: 3821: 3811: 3809: 3800: 3799: 3795: 3750: 3746: 3707: 3703: 3693: 3691: 3678: 3677: 3673: 3663: 3661: 3652: 3651: 3647: 3600: 3596: 3586: 3584: 3571: 3570: 3566: 3535:(19): e016614. 3521: 3514: 3483:(4): CD012395. 3469: 3460: 3411: 3407: 3399: 3385:Table 5-12 in: 3384: 3375: 3330: 3326: 3287: 3283: 3252: 3248: 3201: 3194: 3155: 3148: 3138: 3136: 3093: 3084: 3047: 3043: 3002: 2995: 2980: 2966: 2962: 2917: 2908: 2867: 2850: 2827: 2812: 2759: 2755: 2724: 2717: 2670: 2661: 2622: 2613: 2608: 2604: 2557: 2550: 2511: 2494: 2473:(13): 898–909. 2463: 2432: 2422: 2420: 2405: 2398: 2388: 2386: 2373: 2372: 2363: 2316: 2312: 2267: 2258: 2219: 2188: 2178: 2176: 2163: 2162: 2158: 2127: 2112: 2072: 2066: 2035: 2025: 2023: 2015: 2011: 2010: 2006: 2001: 1984: 1969:(patisiran) or 1965:in the form of 1955: 1915: 1903:people over 110 1888: 1880: 1754: 1673: 1516:Corneodesmosin 919:Fibril protein 849: 842: 839:Congo red stain 824: 815: 805: 796: 793: 784: 781: 772: 769: 760: 757: 748: 745: 736: 730: 721: 718: 703:genetic testing 658:false negatives 627:polarized light 615: 575: 569: 553:enlarged tongue 549: 533:amyloid purpura 529: 486: 443: 437:-like picture. 395: 377: 349: 343: 296: 280: 272:developed world 258:is present, or 238: 213:localized forms 190:spinal stenosis 158:amyloid fibrils 108:Supportive care 79:55–65 years old 22: 17: 12: 11: 5: 4890: 4880: 4879: 4874: 4869: 4852: 4851: 4848: 4847: 4845: 4844: 4839: 4834: 4828: 4827: 4822: 4816: 4815: 4810: 4804: 4802: 4796: 4795: 4793: 4792: 4787: 4781: 4779: 4773: 4772: 4770: 4769: 4763: 4761: 4755: 4754: 4752: 4751: 4746: 4741: 4735: 4733: 4727: 4726: 4721: 4719: 4710: 4704: 4703: 4701: 4700: 4695: 4690: 4685: 4680: 4678:AA amyloidosis 4675: 4673:AL amyloidosis 4669: 4667: 4663: 4662: 4660: 4659: 4654: 4649: 4644: 4639: 4634: 4629: 4620: 4615: 4610: 4605: 4599: 4597: 4589: 4588: 4581: 4580: 4573: 4566: 4558: 4549: 4548: 4545: 4544: 4533: 4521: 4520: 4518: 4514: 4513: 4510: 4509: 4498: 4487: 4472: 4456: 4451: 4450: 4448: 4447:Classification 4441: 4440: 4429: 4428:External links 4426: 4423: 4422: 4393:(4): 194–201. 4370: 4339: 4296: 4247: 4200:(3): 232–239. 4180: 4131: 4085: 4059: 4024: 3995:(6): 375–383. 3972: 3928: 3879: 3849: 3819: 3793: 3764:(6): 493–502. 3744: 3701: 3671: 3645: 3594: 3564: 3512: 3458: 3405: 3397: 3373: 3344:(4): 217–222. 3324: 3297:(3): 162–176. 3281: 3246: 3192: 3146: 3082: 3041: 2993: 2978: 2960: 2906: 2848: 2810: 2773:(6): 895–905. 2753: 2734:(3): 597–612. 2715: 2659: 2632:(5): 578–588. 2611: 2602: 2548: 2521:(3): 776–787. 2492: 2430: 2396: 2361: 2310: 2281:(4): 322–334. 2256: 2186: 2156: 2110: 2083:(2): 323–345. 2033: 2003: 2002: 2000: 1997: 1996: 1995: 1990: 1983: 1980: 1954: 1951: 1933:bronchiectasis 1914: 1911: 1905:who have been 1887: 1884: 1879: 1878:Support groups 1876: 1753: 1750: 1734: 1733: 1722: 1708: 1707: 1680: 1672: 1669: 1666: 1665: 1662: 1659: 1656: 1650: 1646: 1645: 1642: 1639: 1636: 1633: 1629: 1628: 1625: 1622: 1619: 1616: 1612: 1611: 1608: 1605: 1602: 1601:Semenogelin 1 1599: 1595: 1594: 1591: 1588: 1585: 1582: 1578: 1577: 1574: 1571: 1568: 1565: 1561: 1560: 1557: 1554: 1551: 1548: 1544: 1543: 1540: 1537: 1534: 1531: 1527: 1526: 1523: 1520: 1517: 1514: 1510: 1509: 1506: 1503: 1500: 1497: 1493: 1492: 1489: 1486: 1483: 1480: 1476: 1475: 1472: 1469: 1466: 1463: 1459: 1458: 1455: 1452: 1451:Cardiac atria 1449: 1446: 1442: 1441: 1438: 1435: 1432: 1429: 1425: 1424: 1418: 1412: 1406: 1403: 1399: 1398: 1389: 1380: 1371: 1362: 1358: 1357: 1354: 1351: 1346: 1343: 1339: 1338: 1335: 1332: 1327: 1324: 1320: 1319: 1313: 1307: 1297: 1291: 1287: 1286: 1283: 1280: 1275: 1272: 1268: 1267: 1264: 1261: 1256: 1253: 1249: 1248: 1245: 1242: 1236: 1233: 1229: 1228: 1225: 1222: 1219: 1216: 1212: 1211: 1208: 1205: 1202: 1199: 1195: 1194: 1191: 1188: 1185: 1182: 1178: 1177: 1174: 1171: 1168: 1165: 1161: 1160: 1157: 1154: 1151: 1148: 1144: 1143: 1140: 1137: 1134: 1131: 1127: 1126: 1123: 1120: 1117: 1114: 1110: 1109: 1106: 1103: 1100: 1094: 1090: 1089: 1086: 1083: 1077: 1071: 1067: 1066: 1060: 1054: 1048: 1036: 1032: 1031: 1025: 1019: 1013: 1001: 997: 996: 993: 990: 984: 981: 977: 976: 973: 970: 964: 959: 955: 954: 951: 948: 942: 937: 933: 932: 929: 926: 925:Target Organs 923: 920: 904:AA amyloidosis 892:AL amyloidosis 848: 847:Classification 845: 844: 843: 825: 818: 816: 806: 799: 797: 794: 787: 785: 782: 775: 773: 770: 763: 761: 758: 751: 749: 746: 739: 737: 731: 724: 722: 719: 712: 614: 611: 571:Main article: 568: 565: 548: 545: 528: 525: 485: 482: 455:hypothyroidism 451:adrenal glands 442: 439: 427:AL amyloidosis 394: 391: 376: 375:Nervous system 373: 345:Main article: 342: 339: 315:plasma protein 295: 292: 279: 276: 236: 217:systemic forms 145: 144: 141: 137: 136: 133: 129: 128: 125: 119: 118: 105: 101: 100: 95: 89: 88: 85: 81: 80: 77: 73: 72: 69: 63: 62: 57: 51: 50: 38: 37: 29: 28: 20: 15: 9: 6: 4: 3: 2: 4889: 4878: 4875: 4873: 4870: 4868: 4865: 4864: 4862: 4843: 4840: 4838: 4835: 4833: 4830: 4829: 4826: 4823: 4821: 4818: 4817: 4814: 4811: 4809: 4806: 4805: 4803: 4801: 4797: 4791: 4788: 4786: 4783: 4782: 4780: 4778: 4774: 4768: 4765: 4764: 4762: 4760: 4756: 4750: 4747: 4745: 4742: 4740: 4737: 4736: 4734: 4732: 4728: 4724: 4720: 4718: 4714: 4711: 4709: 4705: 4699: 4696: 4694: 4691: 4689: 4686: 4684: 4681: 4679: 4676: 4674: 4671: 4670: 4668: 4664: 4658: 4655: 4653: 4650: 4648: 4645: 4643: 4640: 4638: 4635: 4633: 4630: 4628: 4624: 4621: 4619: 4616: 4614: 4611: 4609: 4606: 4604: 4601: 4600: 4598: 4595: 4590: 4586: 4579: 4574: 4572: 4567: 4565: 4560: 4559: 4556: 4543: 4539: 4538: 4534: 4532: 4528: 4527: 4523: 4522: 4519: 4515: 4508: 4504: 4503: 4499: 4497: 4493: 4492: 4488: 4486: 4482: 4481: 4477: 4473: 4471: 4467: 4466: 4462: 4458: 4457: 4454: 4449: 4445: 4439: 4435: 4432: 4431: 4418: 4414: 4409: 4404: 4400: 4396: 4392: 4388: 4384: 4377: 4375: 4358: 4354: 4350: 4343: 4335: 4331: 4327: 4323: 4319: 4315: 4311: 4307: 4300: 4292: 4288: 4283: 4278: 4274: 4270: 4266: 4262: 4258: 4251: 4235: 4231: 4227: 4223: 4219: 4215: 4211: 4207: 4203: 4199: 4195: 4191: 4184: 4176: 4172: 4168: 4164: 4159: 4154: 4150: 4146: 4142: 4135: 4127: 4123: 4119: 4115: 4111: 4107: 4103: 4099: 4092: 4090: 4073: 4069: 4063: 4055: 4051: 4047: 4043: 4039: 4035: 4028: 4020: 4016: 4012: 4008: 4003: 3998: 3994: 3990: 3986: 3979: 3977: 3968: 3964: 3959: 3954: 3950: 3946: 3942: 3935: 3933: 3924: 3920: 3915: 3910: 3906: 3902: 3898: 3894: 3890: 3883: 3867: 3863: 3859: 3853: 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2263: 2261: 2252: 2248: 2244: 2240: 2236: 2232: 2228: 2224: 2217: 2215: 2213: 2211: 2209: 2207: 2205: 2203: 2201: 2199: 2197: 2195: 2193: 2191: 2174: 2170: 2166: 2160: 2152: 2148: 2144: 2140: 2136: 2132: 2125: 2123: 2121: 2119: 2117: 2115: 2106: 2102: 2098: 2094: 2090: 2086: 2082: 2078: 2071: 2064: 2062: 2060: 2058: 2056: 2054: 2052: 2050: 2048: 2046: 2044: 2042: 2040: 2038: 2021: 2014: 2008: 2004: 1994: 1993:Proteinopathy 1991: 1989: 1986: 1985: 1979: 1975: 1972: 1968: 1964: 1960: 1950: 1948: 1947:heart failure 1943: 1940: 1938: 1934: 1930: 1929:osteomyelitis 1926: 1921: 1918: 1910: 1908: 1904: 1899: 1895: 1892: 1883: 1875: 1873: 1869: 1865: 1863: 1858: 1855: 1852: 1848: 1845: 1839: 1837: 1832: 1830: 1826: 1822: 1818: 1814: 1813:heart failure 1810: 1805: 1803: 1802:interleukin-6 1799: 1795: 1791: 1787: 1786:Interleukin-1 1783: 1779: 1775: 1770: 1767: 1763: 1759: 1749: 1747: 1743: 1739: 1731: 1727: 1723: 1720: 1716: 1713: 1712: 1711: 1705: 1701: 1697: 1693: 1689: 1685: 1681: 1678: 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620: 610: 607: 603: 599: 594: 592: 588: 587:extracellular 584: 580: 574: 564: 562: 558: 554: 544: 542: 538: 534: 524: 522: 518: 513: 511: 507: 503: 498: 496: 492: 481: 479: 475: 471: 467: 462: 460: 456: 452: 448: 438: 436: 432: 428: 424: 423:Malabsorption 420: 416: 412: 408: 404: 399: 390: 386: 383: 372: 370: 366: 362: 358: 354: 353:heart failure 348: 338: 336: 332: 328: 324: 320: 316: 312: 308: 304: 300: 291: 284: 275: 273: 267: 265: 264:tissue biopsy 261: 257: 253: 248: 246: 242: 234: 230: 226: 222: 218: 214: 210: 205: 203: 199: 195: 191: 187: 183: 179: 175: 171: 167: 163: 159: 155: 151: 142: 138: 134: 130: 126: 124: 120: 117: 113: 109: 106: 102: 99: 98:Tissue biopsy 96: 94: 90: 86: 82: 78: 74: 70: 68: 64: 61: 58: 56: 52: 48: 44: 39: 35: 30: 25: 19: 4584: 4535: 4524: 4500: 4489: 4474: 4459: 4390: 4386: 4361:. 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Retrieved 2019: 2007: 1976: 1956: 1944: 1941: 1925:tuberculosis 1922: 1919: 1916: 1913:Epidemiology 1900: 1896: 1893: 1889: 1881: 1866: 1859: 1856: 1849: 1840: 1833: 1806: 1771: 1762:chemotherapy 1755: 1735: 1709: 1674: 1653: 1635:Cathepsin K 1618:Enfurvitide 1567:Lactoferrin 1533:Lactadherin 1421: 1415: 1409: 1395: 1392: 1386: 1383: 1377: 1374: 1368: 1365: 1326:α-Synuclein 1316: 1310: 1302: 1294: 1241:, PNS, skin 1080: 1063: 1057: 1051: 1042: 1041:, wild type 1028: 1022: 1016: 1007: 1006:, wild type 911: 908: 885: 866: 862: 850: 707: 695: 688: 669: 662: 647: 635:thioflavin T 616: 595: 576: 567:Pathogenesis 550: 530: 514: 499: 487: 463: 444: 400: 396: 387: 378: 350: 297: 289: 268: 249: 206: 174:palpitations 149: 148: 43:macroglossia 18: 4867:Amyloidosis 4585:Amyloidosis 4542:Amyloidosis 4434:Amyloidosis 4353:www.fda.gov 4151:(1): 1–12. 4078:22 February 3899:(1): 1–12. 3436:2445/108897 3139:25 December 2970:Amyloidosis 2423:29 November 2389:19 November 2137:: 223–241. 1794:canakinumab 1671:Alternative 1621:Iatrogenic 1099:, variants 1076:, variants 1046:, variants 1011:, variants 676:amino acids 602:proteolysis 547:Oral cavity 521:paraparesis 319:proteinuria 166:weight loss 156:, known as 150:Amyloidosis 76:Usual onset 27:Amyloidosis 4861:Categories 4537:Patient UK 4502:DiseasesDB 3262:(1): 1–7. 2837:(1): 1–5. 2571:(1): 221. 1999:References 1959:neuropathy 1868:Vutrisiran 1821:diflunisal 1798:rilonacept 1782:etanercept 1778:infliximab 1700:Calcitonin 1465:Prolactin 854:idiopathic 827:Micrograph 631:microscopy 606:oligomeric 598:beta-sheet 365:sinus node 333:requiring 4820:Pituitary 4800:Endocrine 4526:eMedicine 4363:11 August 4267:(5): 90. 4214:0785-3890 4175:208299494 4126:205541963 3788:235722446 3573:"Tegsedi" 3368:225073269 3215:(1): 47. 3107:(1): 38. 3061:: 41–56. 2988:654382006 2877:: 27–68. 2787:1365-2796 2654:204850185 2305:218600304 2251:220385853 2105:215069282 1971:antisense 1907:autopsied 1886:Prognosis 1851:Patisiran 1844:inotersen 1829:patisiran 1825:inotersen 1809:tafamidis 1766:stem cell 1758:melphalan 1752:Treatment 1147:AApoCIII 881:mutations 879:, due to 877:inherited 858:secondary 654:sensitive 623:Congo red 613:Diagnosis 591:cytosolic 445:Both the 188:, lumbar 132:Frequency 123:Prognosis 104:Treatment 55:Specialty 4832:Pancreas 4531:med/3377 4417:32587078 4357:Archived 4334:49658028 4326:29972750 4291:33993188 4240:18 March 4234:Archived 4230:23446885 4222:18382889 4167:31766892 4118:28277869 4072:Archived 4054:22579241 4019:73419672 4011:30742933 3967:27634125 3923:29222231 3872:15 March 3866:Archived 3842:15 March 3836:Archived 3806:Archived 3780:34215024 3739:52813638 3731:30251172 3688:Archived 3658:Archived 3640:31118583 3587:12 March 3581:Archived 3559:32969287 3507:32311072 3453:18876892 3445:26109736 3360:33100054 3319:31198109 3311:18985467 3276:17223074 3241:22100031 3179:26719234 3133:Archived 3129:53023121 3121:30361521 3077:23896486 3036:Archived 3032:17093068 2955:21483018 2901:28498720 2843:29762107 2805:33274477 2748:27153791 2710:28611935 2646:31639841 2597:30509186 2543:25431033 2535:18076735 2417:Archived 2383:Archived 2356:23425518 2297:32392555 2243:32633805 2179:22 April 2173:Archived 2151:16409147 2097:23597967 1982:See also 1953:Research 1790:anakinra 1776:such as 1746:endoderm 1742:ectoderm 1738:mesoderm 1649:AEFEMP1 1482:Insulin 1130:AApoCII 1113:AApoAIV 1093:AApoAII 890:(termed 873:systemic 643:SAP scan 639:DPD scan 633:. Also, 541:factor X 537:thrombin 466:pancreas 335:dialysis 154:proteins 112:dialysis 67:Symptoms 4808:Thyroid 4594:amyloid 4592:Common 4496:D000686 4408:7335620 4282:8124067 4145:Amyloid 3914:6142527 3812:14 June 3694:20 July 3664:20 July 3631:6507904 3550:7792401 3498:7170468 3338:Amyloid 3232:3228694 3187:4762107 2946:3138545 2796:8248398 2701:5464793 2588:6278059 2487:9302305 2347:3584981 2026:15 June 1698:), and 1570:Cornea 1410:Kidney 1198:ALECT2 1187:Kidney 1153:Kidney 1136:Kidney 1102:Kidney 1070:AApoAI 573:Amyloid 447:thyroid 385:death. 299:Amyloid 294:Kidneys 182:purpura 47:purpura 4759:Kidney 4438:Curlie 4415: 4405: 4332: 4324: 4289: 4279: 4228: 4220: 4212: 4173: 4165: 4124: 4116: 4052: 4017: 4009: 3965: 3921: 3911: 3786: 3778: 3737: 3729: 3638: 3628: 3557: 3547: 3505: 3495: 3451: 3443: 3395: 3366: 3358: 3317: 3309: 3274: 3239: 3229: 3185: 3177: 3159:Lancet 3127: 3119: 3075: 3030: 2986: 2976: 2953: 2943: 2899: 2841: 2803: 2793: 2785: 2746: 2708: 2698: 2678:Cureus 2652: 2644: 2595: 2585: 2541: 2533: 2485: 2354: 2344: 2330:: 31. 2303: 2295: 2249: 2241: 2149: 2103: 2095: 1931:, and 1862:CRISPR 1827:, and 1800:) and 1632:ACatK 1598:ASem1 1581:AOAAP 1428:AIAPP 1323:AαSyn 619:stains 441:Glands 321:) and 303:kidney 200:, and 176:, and 140:Deaths 84:Causes 4731:Brain 4717:Heart 4632:AIAPP 4485:277.3 4330:S2CID 4226:S2CID 4171:S2CID 4122:S2CID 4015:S2CID 3784:S2CID 3735:S2CID 3711:Drugs 3449:S2CID 3364:S2CID 3315:S2CID 3183:S2CID 3125:S2CID 2650:S2CID 2539:S2CID 2301:S2CID 2247:S2CID 2101:S2CID 2073:(PDF) 2016:(PDF) 1615:AEnf 1564:ALac 1547:AKer 1530:AMed 1513:ACor 1502:Lung 1496:ASPC 1479:AIns 1462:APro 1445:AANF 1402:ACal 1361:APrP 1342:ATau 1271:ADan 1252:ABri 1232:ACys 1215:AFib 1181:ALys 1164:AGel 1035:Aβ2M 1000:ATTR 972:S, L 953:A, H 950:S, L 831:heart 682:with 478:cells 435:sprue 341:Heart 4777:Skin 4657:ABri 4652:ACys 4647:AANF 4642:APro 4637:ACal 4613:Aβ2M 4608:ATTR 4491:MeSH 4480:9-CM 4413:PMID 4365:2018 4322:PMID 4287:PMID 4242:2022 4218:PMID 4210:ISSN 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