811:
602:, in response to observed reductions in risk for developing Alzheimer's disease in survivors of these cancers. All cancers were shown to be associated positively with increased Aβ levels, particularly hepatic cancers. This direction of association however has not yet been established. Studies focusing on human breast cancer cell lines have further demonstrated that these cancerous cells display an increased level of expression of amyloid precursor protein.
220:
550:
proteolytic enzymes gamma- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). Aβ circulates in plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) mainly as soluble Aβ40. Amyloid plaques contain both Aβ40 and Aβ42, while vascular amyloid is predominantly the shorter Aβ40. Several sequences of Aβ were found in both lesions.
778:
molecules. Prevention of oligomerization of Aβ has been exemplified by active or passive Aβ immunization. In this process antibodies to Aβ are used to decrease cerebral plaque levels. This is accomplished by promoting microglial clearance and/or redistributing the peptide from the brain to systemic circulation. Antibodies that target Aβ and were tested in clinical trials included
561:
of both familial and sporadic
Alzheimer's disease. Due to its more hydrophobic nature, the Aβ42 is the most amyloidogenic form of the peptide. However the central sequence KLVFFAE is known to form amyloid on its own, and probably forms the core of the fibril. One study further correlated Aβ42 levels
755:
molecular dynamics studies suggested that amyloid beta can indeed populate multiple discrete structural states; more recent studies identified a multiplicity of discrete conformational clusters by statistical analysis. By NMR-guided simulations, amyloid beta 1-40 and amyloid beta 1-42 also seem to
549:
and vascular amyloid; it contributes to cerebrovascular lesions and is neurotoxic. It is unresolved how Aβ accumulates in the central nervous system and subsequently initiates the disease of cells. Significant efforts have been focused on the mechanisms responsible for Aβ production, including the
759:
Low-temperature and low-salt conditions allowed to isolate pentameric disc-shaped oligomers devoid of beta structure. In contrast, soluble oligomers prepared in the presence of detergents seem to feature substantial beta sheet content with mixed parallel and antiparallel character, different from
777:
may stimulate the host immune system to recognize and attack Aβ, or provide antibodies that either prevent plaque deposition or enhance clearance of plaques or Aβ oligomers. Oligomerization is a chemical process that converts individual molecules into a chain consisting of a finite number of
481:
clears metabolic waste from the mammalian brain, and in particular amyloid beta. A number of proteases have been implicated by both genetic and biochemical studies as being responsible for the recognition and degradation of amyloid beta; these include insulin degrading enzyme and presequence
895:
is a label-free method that measures the vibration of molecules in tissue samples. Amyloid proteins like Aβ can be detected with this technique because of their high content of β-sheet structures. Recently, the formation of Aβ fibrils was resolved in different
450:
The normal function of Aβ is not yet known. Though some animal studies have shown that the absence of Aβ does not lead to any obvious loss of physiological function, several potential activities have been discovered for Aβ, including activation of
704:, occurs at codon 717 of the APP gene, and results in a valine to isoleucine amino acid substitution. Histochemical analysis of the APP V717I mutation has revealed extensive Aβ pathology throughout neuroaxis as well as widespread
696:(familial AD, fAD). This form of AD accounts for no more than 10% of all cases, and the vast majority of AD is not accompanied by such mutations. However, familial Alzheimer's disease is likely to result from altered
416:
which may exist in several forms. It is now believed that certain misfolded oligomers (known as "seeds") can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a
910:
is an optical technique which can measure early stages of aggregation by measuring the molecular size and densities as the fibrils elongate. These aggregate processes can also be studied on lipid bilayer constructs.
2881:
Schirinzi T, Di
Lazzaro G, Sancesario GM, Colona VL, Scaricamazza E, Mercuri NB, et al. (December 2017). "Levels of amyloid-beta-42 and CSF pressure are directly related in patients with Alzheimer's disease".
1410:
Luo Y, Bolon B, Damore MA, Fitzpatrick D, Liu H, Zhang J, et al. (October 2003). "BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time".
585:
development, prompting studies on a variety of cancers to elucidate the nature of its possible effects, results are largely inconclusive. Aβ levels have been assessed in relation to a number of cancers, including
3313:
Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, et al. (October 1991). "Early-onset
Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene".
4171:
Gengler S, Gault VA, Harriott P, Hölscher C (June 2007). "Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25-35) are dependent on stimulation-protocol and genetic background".
4215:
Rekas A, Jankova L, Thorn DC, Cappai R, Carver JA (December 2007). "Monitoring the prevention of amyloid fibril formation by alpha-crystallin. Temperature dependence and the nature of the aggregating species".
4135:
Benseny-Cases N, Klementieva O, Cotte M, Ferrer I, Cladera J (December 2014). "Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human
Alzheimer disease brains".
614:
had accumulation of amyloid in association with evidence of
Alzheimer's disease, including declines in cognitive functioning, memory, fine motor movements, executive functioning, and visuospatial skills.
562:
in the brain not only with onset of
Alzheimer's disease, but also reduced cerebrospinal fluid pressure, suggesting that a build-up or inability to clear Aβ42 fragments may play a role into the pathology.
569:" — that the plaques are responsible for the pathology of Alzheimer's disease — is accepted by the majority of researchers, but is not conclusively established. An alternative hypothesis is that amyloid
1771:"Functional activity of the novel Alzheimer's amyloid β-peptide interacting domain (AβID) in the APP and BACE1 promoter sequences and implications in activating apoptotic genes and in amyloidogenesis"
1722:"The Alzheimer's amyloid β-peptide (Aβ) binds a specific DNA Aβ-interacting domain (AβID) in the APP, BACE1, and APOE promoters in a sequence-specific manner: characterizing a new regulatory motif"
3180:
Hartmann T, Bieger SC, Brühl B, Tienari PJ, Ida N, Allsop D, et al. (September 1997). "Distinct sites of intracellular production for
Alzheimer's disease A beta40/42 amyloid peptides".
2925:
Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, et al. (April 2003). "Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis".
3903:
Heurling K, Leuzy A, Zimmer ER, Lubberink M, Nordberg A (February 2016). "Imaging β-amyloid using flutemetamol positron emission tomography: from dosimetry to clinical diagnosis".
31:
3373:(March 1992). "Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology".
482:
protease. The rate of removal is significantly increased during sleep. However, the significance of the glymphatic system in Aβ clearance in
Alzheimer's disease is unknown.
553:
Increases in either total Aβ levels or the relative concentration of both Aβ40 and Aβ42 (where the former is more concentrated in cerebrovascular plaques and the latter in
2531:
Hardy J, Duff K, Hardy KG, Perez-Tur J, Hutton M (September 1998). "Genetic dissection of
Alzheimer's disease and related dementias: amyloid and its relationship to tau".
700:
processing. This is evidenced by the fact that many mutations that lead to fAD occur near γ-secretase cleavage sites on APP. One of the most common mutations causing fAD,
412:. Both neurons and oligodendrocytes produce and release Aβ in the brain, contributing to formation of amyloid plaques. Aβ molecules can aggregate to form flexible soluble
178:
3418:"Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier - phenotypic variability in autosomal dominant Alzheimer's disease"
3733:
Yu L, Edalji R, Harlan JE, Holzman TF, Lopez AP, Labkovsky B, et al. (March 2009). "Structural characterization of a soluble amyloid beta-peptide oligomer".
3502:
Zhang S, Iwata K, Lachenmann MJ, Peng JW, Li S, Stimson ER, et al. (June 2000). "The
Alzheimer's peptide a beta adopts a collapsed coil structure in water".
2734:"The length of amyloid-beta in hereditary cerebral hemorrhage with amyloidosis, Dutch type. Implications for the role of amyloid-beta 1-42 in Alzheimer's disease"
1454:
Bogoyevitch MA, Boehm I, Oakley A, Ketterman AJ, Barr RK (March 2004). "Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential".
1342:
Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: evidence from experimental studies".
701:
1904:"Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer's disease -conformist, nonconformist, and realistic prospects for AD pathogenesis"
2986:
Jin WS, Bu XL, Liu YH, Shen LL, Zhuang ZQ, Jiao SS, et al. (February 2017). "Plasma Amyloid-Beta Levels in Patients with Different Types of Cancer".
3987:
Schmidt SD, Nixon RA, Mathews PM (2012). "Tissue Processing Prior to Analysis of Alzheimer's Disease Associated Proteins and Metabolites, Including Aβ".
1587:
Baruch-Suchodolsky R, Fischer B (May 2009). "Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems".
3588:"Atomic-level characterization of the ensemble of the Aβ(1-42) monomer in water using unbiased molecular dynamics simulations and spectral algorithms"
1673:"Amyloid beta-protein stimulates trafficking of cholesterol and caveolin-1 from the plasma membrane to the Golgi complex in mouse primary astrocytes"
253:
756:
feature highly different conformational states, with the C-terminus of amyloid beta 1-42 being more structured than that of the 1-40 fragment.
122:
110:
3274:"Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect Abeta secretion and APP C-terminal fragment stability"
539:
4456:
3467:
Glenner GG, Wong CW (August 1984). "Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein".
1955:"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β"
1150:
Haass C, Selkoe DJ (February 2007). "Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide".
735:
but rather populates a set of structures. As such, it cannot be crystallized and most structural knowledge on amyloid beta comes from
538:. It is generally believed that Aβ oligomers are the most toxic. Several genetic, cell biology, biochemical and animal studies using
2268:"Label-free vibrational imaging of different Aβ plaque types in Alzheimer's disease reveals sequential events in plaque development"
2775:"beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease"
1540:"A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage"
4625:
4334:
4119:
4045:
4004:
3768:
Strodel B, Lee JW, Whittleston CS, Wales DJ (September 2010). "Transmembrane structures for Alzheimer's Aβ(1-42) oligomers".
1867:
Schluesener HJ, Su Y, Ebrahimi A, Pouladsaz D (June 2012). "Antimicrobial peptides in the brain: neuropeptides and amyloid".
889:, which can visualize nanoscale molecular surfaces, can be used to determine the aggregation state of amyloid beta in vitro.
258:
78:
198:
4441:
429:, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.
4303:
810:
445:
277:
728:
751:
content. However, the most recent (2012) NMR structure of (Aβ 1-40) has significant secondary and tertiary structure.
760:
fibrils; computational studies suggest an antiparallel beta-turn-beta motif instead for membrane-embedded oligomers.
658:
end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 30–51
1101:"Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease"
907:
769:
265:
4640:
534:
Research suggests that soluble oligomeric forms of the amyloid beta may be causative agents in the development of
4635:
1379:"Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner"
397:
2576:"Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE"
654:; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the
186:
4543:
4028:
Schmidt SD, Mazzella MJ, Nixon RA, Mathews PM (2012). "Aβ Measurement by Enzyme-Linked Immunosorbent Assay".
2338:"Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory"
999:
3948:"Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184"
432:
A study has suggested that APP and its amyloid potential is of ancient origins, dating as far back as early
4451:
845:
3637:"The Alzheimer's peptides Abeta40 and 42 adopt distinct conformations in water: a combined MD / NMR study"
4502:
4497:
4481:
3272:
De Jonghe C, Esselens C, Kumar-Singh S, Craessaerts K, Serneels S, Checler F, et al. (August 2001).
861:
705:
503:
270:
4525:
4405:
2165:
Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, et al. (August 2015).
743:. Early NMR-derived models of a 26-aminoacid polypeptide from amyloid beta (Aβ 10–35) show a collapsed
693:
182:
4071:"In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis"
3416:
Lloyd GM, Trejo-Lopez JA, Xia Y, McFarland KN, Lincoln SJ, Ertekin-Taner N, et al. (March 2020).
545:
Brain Aβ is elevated in people with sporadic Alzheimer's disease. Aβ is the main constituent of brain
542:
support the concept that Aβ plays a central role in the development of Alzheimer's disease pathology.
4466:
4385:
4327:
3131:"Characterization of intermediate steps in amyloid beta (Aβ) production under near-native conditions"
2834:"Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease"
687:
628:
238:
91:
4571:
4446:
892:
3586:
Sgourakis NG, Merced-Serrano M, Boutsidis C, Drineas P, Du Z, Wang C, et al. (January 2011).
3539:"Amyloid beta-protein monomer folding: free-energy surfaces reveal alloform-specific differences"
886:
3082:"Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome"
3031:"Amyloid-β precursor protein promotes cell proliferation and motility of advanced breast cancer"
1099:
Rajani RM, Ellingford R, Hellmuth M, Harris SS, Taso OS, Graykowski D, et al. (July 2024).
4507:
2336:
Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. (August 2008).
901:
535:
409:
393:
860:, which also allows one to determine location. Amyloid beta may be primarily vascular, as in
3080:
Hartley SL, Handen BL, Devenny D, Mihaila I, Hardison R, Lao PJ, et al. (October 2017).
2773:
Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, et al. (November 1993).
2659:
Transport-clearance hypothesis for Alzheimer's disease and potential therapeutic implications
2266:
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837:
712:
671:
632:
499:
323:
2621:
Vassar R (December 2002). "Beta-secretase (BACE) as a drug target for Alzheimer's disease".
2574:
Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. (October 1999).
844:), can selectively bind to amyloid beta in vitro and in vivo. This technique, combined with
327:
4645:
4371:
4320:
3323:
2934:
2786:
2732:
Castaño EM, Prelli F, Soto C, Beavis R, Matsubara E, Shoji M, et al. (December 1996).
2686:
2121:
2015:
2004:"Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism"
1818:
Kagan BL, Jang H, Capone R, Teran Arce F, Ramachandran S, Lal R, et al. (April 2012).
1053:
1000:"The amyloid beta peptide: a chemist's perspective. Role in Alzheimer's and fibrillization"
467:
165:
3129:
Olsson F, Schmidt S, Althoff V, Munter LM, Jin S, Rosqvist S, et al. (January 2014).
347:
8:
4650:
4376:
3097:
748:
134:
3327:
2938:
2790:
2690:
2125:
2061:"Molecular basis of substrate recognition and degradation by human presequence protease"
2019:
1377:
Sadigh-Eteghad S, Talebi M, Farhoudi M, EJ Golzari S, Sabermarouf B, Mahmoudi J (2014).
1127:
1100:
1057:
4241:
4197:
3928:
3880:
3853:
3829:
3804:
3710:
3685:
3661:
3636:
3612:
3587:
3563:
3538:
3444:
3417:
3398:
3347:
3254:
3205:
3157:
3130:
3106:
3081:
3057:
3030:
3011:
2968:
2907:
2858:
2833:
2603:
2556:
2513:
2416:
2389:
2362:
2337:
2317:
Parker MH, Reitz AB (2000). "Assembly of β-Amyloid Aggregates at the Molecular Level".
2294:
2267:
2240:
2215:
2191:
2166:
2142:
2109:
2085:
2060:
2036:
2003:
1979:
1954:
1930:
1903:
1844:
1819:
1795:
1770:
1746:
1721:
1697:
1688:
1672:
1653:
1564:
1555:
1539:
1515:
1490:
1436:
1319:
1292:
1268:
1243:
1219:
1194:
1175:
1076:
1041:
975:
950:
740:
566:
115:
35:
A partially folded structure of amyloid beta(1 40) in an aqueous environment (pdb 2lfm)
4261:"Insight into early events in the aggregation of the prion protein on lipid membranes"
2849:
2709:
2674:
2634:
2500:
2483:
2457:
1424:
4630:
4282:
4233:
4229:
4189:
4153:
4115:
4092:
4051:
4041:
4010:
4000:
3969:
3946:
Ito H, Shimada H, Shinotoh H, Takano H, Sasaki T, Nogami T, et al. (June 2014).
3920:
3885:
3834:
3785:
3750:
3715:
3666:
3617:
3568:
3519:
3484:
3480:
3449:
3390:
3386:
3339:
3295:
3246:
3197:
3162:
3111:
3062:
3003:
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2899:
2863:
2814:
2809:
2774:
2755:
2714:
2638:
2595:
2548:
2505:
2461:
2421:
2367:
2299:
2245:
2196:
2147:
2090:
2041:
1984:
1953:
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. (August 2012).
1935:
1884:
1849:
1800:
1751:
1702:
1645:
1604:
1569:
1520:
1471:
1428:
1359:
1324:
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1224:
1167:
1132:
1081:
1022:
980:
591:
587:
478:
173:
83:
4245:
4201:
3402:
3258:
2972:
2911:
2673:
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (June 1985).
2607:
2560:
2517:
1657:
1506:
1179:
59:
4558:
4272:
4225:
4181:
4145:
4082:
4033:
3992:
3959:
3932:
3912:
3875:
3865:
3824:
3816:
3777:
3742:
3705:
3697:
3656:
3648:
3607:
3599:
3558:
3550:
3511:
3476:
3439:
3429:
3382:
3351:
3331:
3285:
3236:
3209:
3189:
3152:
3142:
3101:
3093:
3052:
3042:
3015:
2995:
2950:
2942:
2891:
2853:
2845:
2832:
Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, et al. (September 1999).
2804:
2794:
2745:
2704:
2694:
2630:
2587:
2540:
2495:
2453:
2411:
2401:
2357:
2349:
2289:
2279:
2235:
2227:
2214:
Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J (2014).
2186:
2178:
2137:
2129:
2080:
2072:
2031:
2023:
1974:
1966:
1925:
1915:
1876:
1839:
1831:
1790:
1782:
1741:
1733:
1692:
1684:
1635:
1596:
1559:
1551:
1510:
1502:
1463:
1440:
1420:
1390:
1351:
1314:
1304:
1263:
1255:
1214:
1206:
1159:
1122:
1112:
1071:
1061:
1042:"Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol"
1014:
970:
962:
752:
507:
459:
401:
318:
161:
2108:
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. (October 2013).
925:
127:
103:
4600:
4578:
4548:
4361:
4277:
4260:
4037:
3996:
2591:
2059:
King JV, Liang WG, Scherpelz KP, Schilling AB, Meredith SC, Tang WJ (July 2014).
1970:
1467:
1117:
865:
822:
818:
732:
675:
651:
643:
515:
405:
389:
294:
139:
71:
357:
4436:
4431:
3820:
3684:
Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, et al. (May 2010).
3366:
3241:
3224:
3029:
Lim S, Yoo BK, Kim HS, Gilmore HL, Lee Y, Lee HP, et al. (December 2014).
2779:
Proceedings of the National Academy of Sciences of the United States of America
2679:
Proceedings of the National Academy of Sciences of the United States of America
2284:
1786:
1737:
1395:
1378:
1046:
Proceedings of the National Academy of Sciences of the United States of America
966:
599:
491:
4185:
3964:
3947:
3916:
3870:
3652:
3603:
3554:
3434:
2999:
2895:
2657:
2182:
2076:
1920:
1259:
951:"A partially folded structure of amyloid-beta(1-40) in an aqueous environment"
848:
imaging, is used to image areas of plaque deposits in those with Alzheimer's.
4619:
4366:
3686:"Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils"
3370:
3290:
3273:
3047:
2799:
2750:
2733:
2444:
Ghiso J, Frangione B (December 2002). "Amyloidosis and Alzheimer's disease".
1309:
774:
716:
611:
523:
433:
3147:
2946:
2699:
2575:
2133:
1624:"Function of beta-amyloid in cholesterol transport: a lead to neurotoxicity"
1066:
498:
of people with Alzheimer's disease. Aβ can also form the deposits that line
4583:
4381:
4286:
4237:
4193:
4157:
4096:
4087:
4070:
4055:
4014:
3973:
3924:
3889:
3838:
3789:
3754:
3719:
3670:
3621:
3572:
3523:
3515:
3453:
3299:
3250:
3166:
3115:
3066:
3007:
2964:
2903:
2867:
2642:
2599:
2552:
2509:
2465:
2425:
2371:
2303:
2249:
2200:
2151:
2094:
2045:
1988:
1939:
1888:
1853:
1804:
1755:
1706:
1649:
1608:
1573:
1524:
1475:
1432:
1363:
1328:
1277:
1228:
1171:
1136:
1085:
1040:
Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB (August 2021).
1026:
984:
869:
826:
791:
783:
635:
511:
471:
213:
amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)
3488:
3394:
3343:
3201:
2955:
2818:
2759:
2718:
1640:
1623:
1355:
87:
4489:
4475:
4343:
2406:
904:, indicating that plaques transit different stages in their development.
857:
830:
799:
744:
697:
639:
595:
546:
463:
426:
306:
3854:"Passive Aβ Immunotherapy: Current Achievements and Future Perspectives"
3193:
2027:
4595:
4535:
4410:
4395:
3585:
3271:
880:
841:
814:
787:
779:
670:; the longer form is typically produced by cleavage that occurs in the
659:
655:
422:
385:
301:
4149:
3781:
3746:
3701:
2231:
1835:
1600:
1376:
1210:
1018:
4400:
3335:
1241:
795:
624:
3803:
Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K (September 2017).
3312:
2675:"Amyloid plaque core protein in Alzheimer disease and Down syndrome"
2213:
1163:
470:, and anti-microbial activity (potentially associated with Aβ's pro-
4590:
4134:
2880:
2353:
2167:"Clearance systems in the brain-implications for Alzheimer disease"
1491:"Signaling effect of amyloid-beta(42) on the processing of AbetaPP"
570:
558:
413:
66:
2164:
1242:
Pulawski W, Ghoshdastider U, Andrisano V, Filipek S (April 2012).
4566:
4352:
3991:. Methods in Molecular Biology. Vol. 849. pp. 493–506.
2544:
1880:
1489:
Tabaton M, Zhu X, Perry G, Smith MA, Giliberto L (January 2010).
948:
897:
731:, meaning that in solution it does not acquire a unique tertiary
554:
381:
219:
4307:
4032:. Methods in Molecular Biology. Vol. 849. pp. 507–27.
3635:
Sgourakis NG, Yan Y, McCallum SA, Wang C, Garcia AE (May 2007).
282:
4517:
4390:
1453:
949:
Vivekanandan S, Brender JR, Lee SY, Ramamoorthy A (July 2011).
582:
455:
452:
289:
193:
4312:
1866:
1098:
674:, while the shorter form is produced by cleavage in the trans-
4415:
1671:
Igbavboa U, Sun GY, Weisman GA, He Y, Wood WG (August 2009).
1456:
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
920:
876:
519:
495:
418:
30:
4170:
3902:
3415:
4259:
Sanghera N, Swann MJ, Ronan G, Pinheiro TJ (October 2009).
4027:
3364:
3222:
3079:
2672:
2058:
647:
155:
98:
54:
4258:
3905:
European Journal of Nuclear Medicine and Molecular Imaging
3851:
3802:
3767:
3179:
3128:
2573:
2335:
1537:
1341:
522:
associated with protein misfolding disease, also known as
2924:
2002:
Shen Y, Joachimiak A, Rosner MR, Tang WJ (October 2006).
1817:
1586:
1409:
879:
which is an immunosorbent assay which utilizes a pair of
736:
711:
The gene for the amyloid precursor protein is located on
4069:
Stine WB, Dahlgren KN, Krafft GA, LaDu MJ (March 2003).
3945:
3634:
3501:
2772:
2110:"Sleep drives metabolite clearance from the adult brain"
2001:
1769:
Bailey JA, Maloney B, Ge YW, Lahiri DK (November 2011).
4214:
4068:
3852:
Schilling S, Rahfeld JU, Lues I, Lemere CA (May 2018).
2731:
2530:
2216:"Amyloid-beta: a crucial factor in Alzheimer's disease"
1538:
Zou K, Gong JS, Yanagisawa K, Michikawa M (June 2002).
425:. The other protein implicated in Alzheimer's disease,
3805:"Alzheimer's disease drug development pipeline: 2017"
3732:
2265:
1768:
1039:
856:
Amyloid beta can be measured semiquantitatively with
692:
Autosomal-dominant mutations in APP cause hereditary
573:
rather than plaques are responsible for the disease.
3683:
1670:
1488:
851:
638:
of undetermined function. APP can be cleaved by the
446:
Amyloid precursor protein § Biological function
3986:
3469:
Biochemical and Biophysical Research Communications
2831:
1192:
955:
Biochemical and Biophysical Research Communications
944:
942:
719:have a very high incidence of Alzheimer's disease.
662:
residues in length. The most common isoforms are Aβ
408:to yield Aβ in a cholesterol-dependent process and
4265:Biochimica et Biophysica Acta (BBA) - Biomembranes
1952:
2655:
1193:Nussbaum JM, Seward ME, Bloom GS (Jan–Feb 2013).
4617:
3028:
939:
2383:
2381:
2261:
2259:
1901:
1621:
3845:
3365:Lantos PL, Luthert PJ, Hanger D, Anderton BH,
2477:
2475:
2443:
2387:
1820:"Antimicrobial properties of amyloid peptides"
770:Alzheimer's disease § Research directions
4328:
3796:
3628:
3579:
2439:
2437:
2435:
2107:
1719:
506:. The plaques are composed of a tangle of Aβ
4252:
4208:
4164:
4128:
4062:
4021:
3980:
3225:"2008 Alzheimer's disease facts and figures"
3216:
3122:
2985:
2918:
2825:
2614:
2567:
2524:
2378:
2329:
2256:
1946:
1895:
1860:
1811:
1762:
1713:
1664:
1615:
1580:
1531:
1482:
1447:
1403:
4109:
3466:
3173:
2766:
2725:
2666:
2472:
2394:International Journal of Molecular Sciences
2316:
1335:
1290:
1149:
991:
224:Processing of the amyloid precursor protein
4335:
4321:
3536:
2432:
29:
4276:
4086:
3963:
3879:
3869:
3828:
3761:
3709:
3690:Nature Structural & Molecular Biology
3677:
3660:
3611:
3562:
3495:
3443:
3433:
3289:
3240:
3156:
3146:
3105:
3056:
3046:
2954:
2857:
2808:
2798:
2749:
2708:
2698:
2499:
2415:
2405:
2361:
2293:
2283:
2239:
2190:
2141:
2084:
2035:
1978:
1929:
1919:
1843:
1794:
1745:
1696:
1639:
1563:
1514:
1394:
1318:
1308:
1267:
1218:
1195:"Alzheimer disease: a tale of two prions"
1126:
1116:
1075:
1065:
974:
805:
763:
722:
3770:Journal of the American Chemical Society
3530:
2388:Zhao LN, Long HW, Mu Y, Chew LY (2012).
1902:Li H, Liu CC, Zheng H, Huang TY (2018).
809:
510:and regularly ordered aggregates called
1622:Yao ZX, Papadopoulos V (October 2002).
1383:Journal of Medical Hypotheses and Ideas
727:Amyloid beta is commonly thought to be
485:
4618:
3726:
3223:Alzheimer's Association (March 2008).
2662:. Landes Bioscience. pp. 114–122.
2620:
2484:"Clearing the brain's amyloid cobwebs"
2481:
1720:Maloney B, Lahiri DK (November 2011).
1248:Applied Biochemistry and Biotechnology
1152:Nature Reviews. Molecular Cell Biology
997:
529:
494:, extracellular deposits found in the
421:infection. The oligomers are toxic to
4503:ACys+ABri/Cerebral amyloid angiopathy
4457:ATTR/Transthyretin-related hereditary
4316:
2390:"The toxicity of amyloid β oligomers"
1284:
557:plaques) have been implicated in the
518:shared by other peptides such as the
3422:Acta Neuropathologica Communications
3098:10.1016/j.neurobiolaging.2017.05.019
2272:Acta Neuropathologica Communications
4304:Online Mendelian Inheritance in Man
4112:Biomedical Vibrational Spectroscopy
4075:The Journal of Biological Chemistry
3537:Yang M, Teplow DB (December 2008).
3135:The Journal of Biological Chemistry
2738:The Journal of Biological Chemistry
825:(upper left of image) and cerebral
392:found in the brains of people with
388:that are the main component of the
13:
3073:
1689:10.1016/j.neuroscience.2009.04.049
1556:10.1523/JNEUROSCI.22-12-04833.2002
1291:Tharp WG, Sarkar IN (April 2013).
439:
14:
4662:
4297:
2838:The American Journal of Pathology
2656:Zlokovic BV, Frangione B (2003).
852:Post mortem or in tissue biopsies
4230:10.1111/j.1742-4658.2007.06144.x
908:Dual polarisation interferometry
817:showing amyloid beta (brown) in
747:structure devoid of significant
605:
581:While Aβ has been implicated in
218:
4526:AApoA1+AFib+ALys/Familial renal
4452:AA/Familial Mediterranean fever
4342:
4103:
3939:
3896:
3460:
3409:
3358:
3306:
3265:
3022:
2979:
2874:
2649:
2310:
2220:Medical Principles and Practice
2207:
2158:
2101:
2052:
1995:
1908:Translational Neurodegeneration
1507:10.1016/j.expneurol.2009.09.002
1370:
694:early-onset Alzheimer's disease
623:Aβ is formed after sequential
396:. The peptides derive from the
24:Amyloid beta peptide (beta-APP)
2884:Journal of Neural Transmission
2623:Advanced Drug Delivery Reviews
2446:Advanced Drug Delivery Reviews
1959:Science Translational Medicine
1344:Journal of Alzheimer's Disease
1235:
1186:
1143:
1092:
1033:
715:, and accordingly people with
398:amyloid-beta precursor protein
1:
4572:ACal/Medullary thyroid cancer
4544:Primary cutaneous amyloidosis
4442:Aβ2M/Haemodialysis-associated
3504:Journal of Structural Biology
2850:10.1016/S0002-9440(10)65184-X
2635:10.1016/S0169-409X(02)00157-6
2501:10.1016/S0896-6273(01)00475-5
2458:10.1016/S0169-409X(02)00149-7
1425:10.1016/S0969-9961(03)00104-9
932:
893:Vibrational microspectroscopy
883:that recognize amyloid beta.
150:Available protein structures:
4626:Genes on human chromosome 21
4278:10.1016/j.bbamem.2009.08.005
4038:10.1007/978-1-61779-551-0_34
3997:10.1007/978-1-61779-551-0_33
3641:Journal of Molecular Biology
3592:Journal of Molecular Biology
3543:Journal of Molecular Biology
3481:10.1016/0006-291X(84)91209-9
3387:10.1016/0304-3940(92)90408-y
2592:10.1126/science.286.5440.735
2319:Chemtracts-Organic Chemistry
1971:10.1126/scitranslmed.3003748
1468:10.1016/j.bbapap.2003.11.016
1118:10.1371/journal.pbio.3002727
618:
490:Aβ is the main component of
466:transport, functioning as a
7:
4498:Familial amyloid neuropathy
4174:Experimental Brain Research
3952:Journal of Nuclear Medicine
1544:The Journal of Neuroscience
914:
862:cerebral amyloid angiopathy
836:Imaging compounds, notably
706:cerebral amyloid angiopathy
681:
504:cerebral amyloid angiopathy
400:(APP), which is cleaved by
10:
4667:
4110:Lasch P, Kneipp J (2008).
3821:10.1016/j.trci.2017.05.002
3809:Alzheimer's & Dementia
3242:10.1016/j.jalz.2008.02.005
3229:Alzheimer's & Dementia
2482:Selkoe DJ (October 2001).
2285:10.1186/s40478-020-01091-5
1787:10.1016/j.gene.2011.06.017
1738:10.1016/j.gene.2011.06.004
1396:10.1016/j.jmhi.2014.01.001
998:Hamley IW (October 2012).
967:10.1016/j.bbrc.2011.06.133
767:
729:intrinsically unstructured
685:
443:
4557:
4534:
4516:
4488:
4474:
4467:Organ-limited amyloidosis
4465:
4424:
4350:
4186:10.1007/s00221-006-0819-6
3965:10.2967/jnumed.113.133793
3917:10.1007/s00259-015-3208-1
3871:10.3390/molecules23051068
3653:10.1016/j.jmb.2007.02.093
3604:10.1016/j.jmb.2010.10.015
3555:10.1016/j.jmb.2008.09.039
3435:10.1186/s40478-020-0891-3
3000:10.1007/s12640-016-9682-9
2896:10.1007/s00702-017-1786-8
2183:10.1038/nrneurol.2015.119
2171:Nature Reviews. Neurology
2077:10.1016/j.str.2014.05.003
1921:10.1186/s40035-018-0139-3
1260:10.1007/s12010-012-9549-3
688:Amyloid precursor protein
629:amyloid precursor protein
576:
353:
343:
338:
334:
317:
312:
300:
288:
276:
264:
252:
244:
234:
229:
217:
212:
192:
172:
154:
149:
145:
133:
121:
109:
97:
77:
65:
53:
45:
40:
28:
23:
3278:Human Molecular Genetics
3048:10.1186/1471-2407-14-928
2800:10.1073/pnas.90.22.10836
2751:10.1074/jbc.271.50.32185
1310:10.1186/1471-2164-14-290
875:One sensitive method is
3148:10.1074/jbc.M113.498246
2947:10.1126/science.1079469
2700:10.1073/pnas.82.12.4245
2134:10.1126/science.1241224
1869:Frontiers in Bioscience
1824:Molecular Pharmaceutics
1413:Neurobiology of Disease
1067:10.1073/pnas.2102191118
887:Atomic force microscopy
4636:Molecular neuroscience
4508:Aβ/Alzheimer's disease
4088:10.1074/jbc.M210207200
3516:10.1006/jsbi.2000.4288
3291:10.1093/hmg/10.16.1665
2988:Neurotoxicity Research
1495:Experimental Neurology
1293:"Origins of amyloid-β"
833:
829:(right of image) with
806:Measuring amyloid beta
764:Immunotherapy research
723:Structure and toxicity
500:cerebral blood vessels
410:substrate presentation
3086:Neurobiology of Aging
1641:10.1096/fj.02-0285fje
1356:10.3233/JAD-2009-1154
1244:"Ubiquitous amyloids"
838:Pittsburgh compound B
813:
768:Further information:
672:endoplasmic reticulum
458:, protection against
4482:AANF/Isolated atrial
4425:Systemic amyloidosis
4138:Analytical Chemistry
3375:Neuroscience Letters
2407:10.3390/ijms13067303
486:Disease associations
468:transcription factor
4641:Alzheimer's disease
4144:(24): 12047–12054.
4081:(13): 11612–11622.
3776:(38): 13300–13312.
3328:1991Natur.353..844C
3194:10.1038/nm0997-1016
2939:2003Sci...300..486K
2791:1993PNAS...9010836R
2785:(22): 10836–10840.
2744:(50): 32185–32191.
2691:1985PNAS...82.4245M
2533:Nature Neuroscience
2126:2013Sci...342..373X
2028:10.1038/nature05143
2020:2006Natur.443..870S
1058:2021PNAS..11802191W
1052:(33): e2102191118.
902:Alzheimer's disease
749:secondary structure
540:experimental models
536:Alzheimer's disease
530:Alzheimer's disease
394:Alzheimer's disease
834:
741:molecular dynamics
567:amyloid hypothesis
4613:
4612:
4609:
4608:
4584:APro/Prolactinoma
4447:AGel/Finnish type
4271:(10): 2245–2251.
4224:(24): 6290–6304.
4150:10.1021/ac502667b
4121:978-0-470-22945-3
4047:978-1-61779-550-3
4006:978-1-61779-550-3
3782:10.1021/ja103725c
3747:10.1021/bi802046n
3702:10.1038/nsmb.1799
3322:(6347): 844–846.
3284:(16): 1665–1671.
2933:(5618): 486–489.
2890:(12): 1621–1625.
2685:(12): 4245–4249.
2629:(12): 1589–1602.
2586:(5440): 735–741.
2452:(12): 1539–1551.
2232:10.1159/000369101
2120:(6156): 373–377.
2014:(7113): 870–874.
1965:(147): 147ra111.
1836:10.1021/mp200419b
1634:(12): 1677–1679.
1601:10.1021/bi802361k
1595:(20): 4354–4370.
1550:(12): 4833–4841.
1211:10.4161/pri.22118
1019:10.1021/cr3000994
1013:(10): 5147–5192.
840:, (6-OH-BTA-1, a
479:glymphatic system
367:
366:
363:
362:
208:
207:
204:
203:
199:structure summary
16:Group of peptides
4658:
4596:AIAPP/Insulinoma
4472:
4471:
4355:forming proteins
4337:
4330:
4323:
4314:
4313:
4291:
4290:
4280:
4256:
4250:
4249:
4218:The FEBS Journal
4212:
4206:
4205:
4168:
4162:
4161:
4132:
4126:
4125:
4107:
4101:
4100:
4090:
4066:
4060:
4059:
4030:Amyloid Proteins
4025:
4019:
4018:
3989:Amyloid Proteins
3984:
3978:
3977:
3967:
3943:
3937:
3936:
3900:
3894:
3893:
3883:
3873:
3849:
3843:
3842:
3832:
3800:
3794:
3793:
3765:
3759:
3758:
3741:(9): 1870–1877.
3730:
3724:
3723:
3713:
3681:
3675:
3674:
3664:
3647:(5): 1448–1457.
3632:
3626:
3625:
3615:
3583:
3577:
3576:
3566:
3534:
3528:
3527:
3510:(2–3): 130–141.
3499:
3493:
3492:
3475:(3): 1131–1135.
3464:
3458:
3457:
3447:
3437:
3413:
3407:
3406:
3362:
3356:
3355:
3336:10.1038/353844a0
3310:
3304:
3303:
3293:
3269:
3263:
3262:
3244:
3220:
3214:
3213:
3188:(9): 1016–1020.
3177:
3171:
3170:
3160:
3150:
3141:(3): 1540–1550.
3126:
3120:
3119:
3109:
3077:
3071:
3070:
3060:
3050:
3026:
3020:
3019:
2983:
2977:
2976:
2958:
2922:
2916:
2915:
2878:
2872:
2871:
2861:
2829:
2823:
2822:
2812:
2802:
2770:
2764:
2763:
2753:
2729:
2723:
2722:
2712:
2702:
2670:
2664:
2663:
2653:
2647:
2646:
2618:
2612:
2611:
2571:
2565:
2564:
2528:
2522:
2521:
2503:
2479:
2470:
2469:
2441:
2430:
2429:
2419:
2409:
2400:(6): 7303–7327.
2385:
2376:
2375:
2365:
2333:
2327:
2326:
2314:
2308:
2307:
2297:
2287:
2263:
2254:
2253:
2243:
2211:
2205:
2204:
2194:
2162:
2156:
2155:
2145:
2105:
2099:
2098:
2088:
2056:
2050:
2049:
2039:
1999:
1993:
1992:
1982:
1950:
1944:
1943:
1933:
1923:
1899:
1893:
1892:
1875:(4): 1375–1380.
1864:
1858:
1857:
1847:
1815:
1809:
1808:
1798:
1766:
1760:
1759:
1749:
1717:
1711:
1710:
1700:
1668:
1662:
1661:
1643:
1619:
1613:
1612:
1584:
1578:
1577:
1567:
1535:
1529:
1528:
1518:
1486:
1480:
1479:
1451:
1445:
1444:
1407:
1401:
1400:
1398:
1374:
1368:
1367:
1339:
1333:
1332:
1322:
1312:
1288:
1282:
1281:
1271:
1254:(7): 1626–1643.
1239:
1233:
1232:
1222:
1190:
1184:
1183:
1147:
1141:
1140:
1130:
1120:
1096:
1090:
1089:
1079:
1069:
1037:
1031:
1030:
1007:Chemical Reviews
1004:
995:
989:
988:
978:
946:
753:Replica exchange
462:, regulation of
460:oxidative stress
336:
335:
222:
210:
209:
147:
146:
33:
21:
20:
4666:
4665:
4661:
4660:
4659:
4657:
4656:
4655:
4616:
4615:
4614:
4605:
4601:Type 2 diabetes
4553:
4549:Amyloid purpura
4530:
4512:
4484:
4461:
4420:
4346:
4341:
4300:
4295:
4294:
4257:
4253:
4213:
4209:
4169:
4165:
4133:
4129:
4122:
4108:
4104:
4067:
4063:
4048:
4026:
4022:
4007:
3985:
3981:
3944:
3940:
3901:
3897:
3850:
3846:
3801:
3797:
3766:
3762:
3731:
3727:
3682:
3678:
3633:
3629:
3584:
3580:
3535:
3531:
3500:
3496:
3465:
3461:
3414:
3410:
3363:
3359:
3311:
3307:
3270:
3266:
3221:
3217:
3182:Nature Medicine
3178:
3174:
3127:
3123:
3078:
3074:
3027:
3023:
2984:
2980:
2923:
2919:
2879:
2875:
2830:
2826:
2771:
2767:
2730:
2726:
2671:
2667:
2654:
2650:
2619:
2615:
2572:
2568:
2529:
2525:
2480:
2473:
2442:
2433:
2386:
2379:
2342:Nature Medicine
2334:
2330:
2315:
2311:
2264:
2257:
2212:
2208:
2163:
2159:
2106:
2102:
2071:(7): 996–1007.
2057:
2053:
2000:
1996:
1951:
1947:
1900:
1896:
1865:
1861:
1816:
1812:
1767:
1763:
1718:
1714:
1669:
1665:
1620:
1616:
1585:
1581:
1536:
1532:
1487:
1483:
1462:(1–2): 89–101.
1452:
1448:
1408:
1404:
1375:
1371:
1340:
1336:
1289:
1285:
1240:
1236:
1191:
1187:
1164:10.1038/nrm2101
1148:
1144:
1111:(7): e3002727.
1097:
1093:
1038:
1034:
1002:
996:
992:
947:
940:
935:
917:
866:amyloid plaques
854:
823:cerebral cortex
819:amyloid plaques
808:
772:
766:
725:
702:London Mutation
690:
684:
669:
665:
621:
608:
579:
532:
512:amyloid fibrils
492:amyloid plaques
488:
448:
442:
440:Normal function
406:gamma secretase
390:amyloid plaques
225:
111:OPM superfamily
36:
17:
12:
11:
5:
4664:
4654:
4653:
4648:
4643:
4638:
4633:
4628:
4611:
4610:
4607:
4606:
4604:
4603:
4598:
4593:
4587:
4586:
4581:
4575:
4574:
4569:
4563:
4561:
4555:
4554:
4552:
4551:
4546:
4540:
4538:
4532:
4531:
4529:
4528:
4522:
4520:
4514:
4513:
4511:
4510:
4505:
4500:
4494:
4492:
4486:
4485:
4480:
4478:
4469:
4463:
4462:
4460:
4459:
4454:
4449:
4444:
4439:
4437:AA amyloidosis
4434:
4432:AL amyloidosis
4428:
4426:
4422:
4421:
4419:
4418:
4413:
4408:
4403:
4398:
4393:
4388:
4379:
4374:
4369:
4364:
4358:
4356:
4348:
4347:
4340:
4339:
4332:
4325:
4317:
4311:
4310:
4299:
4298:External links
4296:
4293:
4292:
4251:
4207:
4180:(4): 621–630.
4163:
4127:
4120:
4102:
4061:
4046:
4020:
4005:
3979:
3958:(6): 932–938.
3938:
3911:(2): 362–373.
3895:
3844:
3815:(3): 367–384.
3795:
3760:
3725:
3696:(5): 561–567.
3676:
3627:
3598:(2): 570–583.
3578:
3549:(2): 450–464.
3529:
3494:
3459:
3408:
3381:(2): 221–224.
3357:
3305:
3264:
3235:(2): 110–133.
3215:
3172:
3121:
3072:
3021:
2994:(2): 283–288.
2978:
2956:2027.42/150615
2917:
2873:
2844:(3): 853–862.
2824:
2765:
2724:
2665:
2648:
2613:
2566:
2539:(5): 355–358.
2523:
2494:(2): 177–180.
2471:
2431:
2377:
2354:10.1038/nm1782
2348:(8): 837–842.
2328:
2309:
2255:
2206:
2177:(8): 457–470.
2157:
2100:
2051:
1994:
1945:
1894:
1859:
1830:(4): 708–717.
1810:
1781:(1–2): 13–22.
1761:
1712:
1683:(2): 328–338.
1663:
1614:
1579:
1530:
1481:
1446:
1402:
1369:
1350:(2): 401–412.
1334:
1283:
1234:
1185:
1158:(2): 101–112.
1142:
1091:
1032:
990:
961:(2): 312–316.
937:
936:
934:
931:
930:
929:
923:
916:
913:
858:immunostaining
853:
850:
831:immunostaining
807:
804:
765:
762:
724:
721:
683:
680:
667:
663:
620:
617:
607:
604:
578:
575:
531:
528:
487:
484:
441:
438:
402:beta secretase
365:
364:
361:
360:
355:
351:
350:
345:
341:
340:
332:
331:
321:
315:
314:
310:
309:
304:
298:
297:
292:
286:
285:
280:
274:
273:
268:
262:
261:
256:
250:
249:
246:
242:
241:
236:
232:
231:
227:
226:
223:
215:
214:
206:
205:
202:
201:
196:
190:
189:
176:
170:
169:
159:
152:
151:
143:
142:
137:
131:
130:
125:
119:
118:
113:
107:
106:
101:
95:
94:
81:
75:
74:
69:
63:
62:
57:
51:
50:
47:
43:
42:
38:
37:
34:
26:
25:
15:
9:
6:
4:
3:
2:
4663:
4652:
4649:
4647:
4644:
4642:
4639:
4637:
4634:
4632:
4629:
4627:
4624:
4623:
4621:
4602:
4599:
4597:
4594:
4592:
4589:
4588:
4585:
4582:
4580:
4577:
4576:
4573:
4570:
4568:
4565:
4564:
4562:
4560:
4556:
4550:
4547:
4545:
4542:
4541:
4539:
4537:
4533:
4527:
4524:
4523:
4521:
4519:
4515:
4509:
4506:
4504:
4501:
4499:
4496:
4495:
4493:
4491:
4487:
4483:
4479:
4477:
4473:
4470:
4468:
4464:
4458:
4455:
4453:
4450:
4448:
4445:
4443:
4440:
4438:
4435:
4433:
4430:
4429:
4427:
4423:
4417:
4414:
4412:
4409:
4407:
4404:
4402:
4399:
4397:
4394:
4392:
4389:
4387:
4383:
4380:
4378:
4375:
4373:
4370:
4368:
4365:
4363:
4360:
4359:
4357:
4354:
4349:
4345:
4338:
4333:
4331:
4326:
4324:
4319:
4318:
4315:
4309:
4305:
4302:
4301:
4288:
4284:
4279:
4274:
4270:
4266:
4262:
4255:
4247:
4243:
4239:
4235:
4231:
4227:
4223:
4219:
4211:
4203:
4199:
4195:
4191:
4187:
4183:
4179:
4175:
4167:
4159:
4155:
4151:
4147:
4143:
4139:
4131:
4123:
4117:
4113:
4106:
4098:
4094:
4089:
4084:
4080:
4076:
4072:
4065:
4057:
4053:
4049:
4043:
4039:
4035:
4031:
4024:
4016:
4012:
4008:
4002:
3998:
3994:
3990:
3983:
3975:
3971:
3966:
3961:
3957:
3953:
3949:
3942:
3934:
3930:
3926:
3922:
3918:
3914:
3910:
3906:
3899:
3891:
3887:
3882:
3877:
3872:
3867:
3863:
3859:
3855:
3848:
3840:
3836:
3831:
3826:
3822:
3818:
3814:
3810:
3806:
3799:
3791:
3787:
3783:
3779:
3775:
3771:
3764:
3756:
3752:
3748:
3744:
3740:
3736:
3729:
3721:
3717:
3712:
3707:
3703:
3699:
3695:
3691:
3687:
3680:
3672:
3668:
3663:
3658:
3654:
3650:
3646:
3642:
3638:
3631:
3623:
3619:
3614:
3609:
3605:
3601:
3597:
3593:
3589:
3582:
3574:
3570:
3565:
3560:
3556:
3552:
3548:
3544:
3540:
3533:
3525:
3521:
3517:
3513:
3509:
3505:
3498:
3490:
3486:
3482:
3478:
3474:
3470:
3463:
3455:
3451:
3446:
3441:
3436:
3431:
3427:
3423:
3419:
3412:
3404:
3400:
3396:
3392:
3388:
3384:
3380:
3376:
3372:
3368:
3361:
3353:
3349:
3345:
3341:
3337:
3333:
3329:
3325:
3321:
3317:
3309:
3301:
3297:
3292:
3287:
3283:
3279:
3275:
3268:
3260:
3256:
3252:
3248:
3243:
3238:
3234:
3230:
3226:
3219:
3211:
3207:
3203:
3199:
3195:
3191:
3187:
3183:
3176:
3168:
3164:
3159:
3154:
3149:
3144:
3140:
3136:
3132:
3125:
3117:
3113:
3108:
3103:
3099:
3095:
3091:
3087:
3083:
3076:
3068:
3064:
3059:
3054:
3049:
3044:
3040:
3036:
3032:
3025:
3017:
3013:
3009:
3005:
3001:
2997:
2993:
2989:
2982:
2974:
2970:
2966:
2962:
2957:
2952:
2948:
2944:
2940:
2936:
2932:
2928:
2921:
2913:
2909:
2905:
2901:
2897:
2893:
2889:
2885:
2877:
2869:
2865:
2860:
2855:
2851:
2847:
2843:
2839:
2835:
2828:
2820:
2816:
2811:
2806:
2801:
2796:
2792:
2788:
2784:
2780:
2776:
2769:
2761:
2757:
2752:
2747:
2743:
2739:
2735:
2728:
2720:
2716:
2711:
2706:
2701:
2696:
2692:
2688:
2684:
2680:
2676:
2669:
2661:
2660:
2652:
2644:
2640:
2636:
2632:
2628:
2624:
2617:
2609:
2605:
2601:
2597:
2593:
2589:
2585:
2581:
2577:
2570:
2562:
2558:
2554:
2550:
2546:
2542:
2538:
2534:
2527:
2519:
2515:
2511:
2507:
2502:
2497:
2493:
2489:
2485:
2478:
2476:
2467:
2463:
2459:
2455:
2451:
2447:
2440:
2438:
2436:
2427:
2423:
2418:
2413:
2408:
2403:
2399:
2395:
2391:
2384:
2382:
2373:
2369:
2364:
2359:
2355:
2351:
2347:
2343:
2339:
2332:
2324:
2320:
2313:
2305:
2301:
2296:
2291:
2286:
2281:
2277:
2273:
2269:
2262:
2260:
2251:
2247:
2242:
2237:
2233:
2229:
2225:
2221:
2217:
2210:
2202:
2198:
2193:
2188:
2184:
2180:
2176:
2172:
2168:
2161:
2153:
2149:
2144:
2139:
2135:
2131:
2127:
2123:
2119:
2115:
2111:
2104:
2096:
2092:
2087:
2082:
2078:
2074:
2070:
2066:
2062:
2055:
2047:
2043:
2038:
2033:
2029:
2025:
2021:
2017:
2013:
2009:
2005:
1998:
1990:
1986:
1981:
1976:
1972:
1968:
1964:
1960:
1956:
1949:
1941:
1937:
1932:
1927:
1922:
1917:
1913:
1909:
1905:
1898:
1890:
1886:
1882:
1878:
1874:
1870:
1863:
1855:
1851:
1846:
1841:
1837:
1833:
1829:
1825:
1821:
1814:
1806:
1802:
1797:
1792:
1788:
1784:
1780:
1776:
1772:
1765:
1757:
1753:
1748:
1743:
1739:
1735:
1732:(1–2): 1–12.
1731:
1727:
1723:
1716:
1708:
1704:
1699:
1694:
1690:
1686:
1682:
1678:
1674:
1667:
1659:
1655:
1651:
1647:
1642:
1637:
1633:
1629:
1628:FASEB Journal
1625:
1618:
1610:
1606:
1602:
1598:
1594:
1590:
1583:
1575:
1571:
1566:
1561:
1557:
1553:
1549:
1545:
1541:
1534:
1526:
1522:
1517:
1512:
1508:
1504:
1500:
1496:
1492:
1485:
1477:
1473:
1469:
1465:
1461:
1457:
1450:
1442:
1438:
1434:
1430:
1426:
1422:
1418:
1414:
1406:
1397:
1392:
1388:
1384:
1380:
1373:
1365:
1361:
1357:
1353:
1349:
1345:
1338:
1330:
1326:
1321:
1316:
1311:
1306:
1302:
1298:
1294:
1287:
1279:
1275:
1270:
1265:
1261:
1257:
1253:
1249:
1245:
1238:
1230:
1226:
1221:
1216:
1212:
1208:
1204:
1200:
1196:
1189:
1181:
1177:
1173:
1169:
1165:
1161:
1157:
1153:
1146:
1138:
1134:
1129:
1124:
1119:
1114:
1110:
1106:
1102:
1095:
1087:
1083:
1078:
1073:
1068:
1063:
1059:
1055:
1051:
1047:
1043:
1036:
1028:
1024:
1020:
1016:
1012:
1008:
1001:
994:
986:
982:
977:
972:
968:
964:
960:
956:
952:
945:
943:
938:
927:
926:Sylvain Lesné
924:
922:
919:
918:
912:
909:
905:
903:
899:
894:
890:
888:
884:
882:
878:
873:
871:
867:
863:
859:
849:
847:
843:
839:
832:
828:
827:blood vessels
824:
820:
816:
812:
803:
801:
797:
793:
789:
785:
781:
776:
775:Immunotherapy
771:
761:
757:
754:
750:
746:
742:
738:
734:
730:
720:
718:
717:Down syndrome
714:
713:chromosome 21
709:
707:
703:
699:
695:
689:
679:
677:
673:
661:
657:
653:
649:
645:
641:
637:
634:
633:transmembrane
630:
626:
616:
613:
612:Down syndrome
606:Down syndrome
603:
601:
597:
593:
589:
584:
574:
572:
568:
563:
560:
556:
551:
548:
543:
541:
537:
527:
525:
524:proteinopathy
521:
517:
513:
509:
505:
501:
497:
493:
483:
480:
475:
473:
469:
465:
461:
457:
454:
447:
437:
435:
434:deuterostomes
430:
428:
424:
420:
415:
411:
407:
403:
399:
395:
391:
387:
383:
379:
375:
371:
359:
356:
352:
349:
346:
342:
337:
333:
330:
329:
325:
322:
320:
316:
311:
308:
305:
303:
299:
296:
293:
291:
287:
284:
281:
279:
275:
272:
269:
267:
263:
260:
257:
255:
251:
247:
243:
240:
237:
233:
228:
221:
216:
211:
200:
197:
195:
191:
188:
184:
180:
177:
175:
171:
167:
163:
160:
157:
153:
148:
144:
141:
138:
136:
132:
129:
126:
124:
120:
117:
114:
112:
108:
105:
102:
100:
96:
93:
89:
85:
82:
80:
76:
73:
70:
68:
64:
61:
58:
56:
52:
48:
44:
39:
32:
27:
22:
19:
4268:
4264:
4254:
4221:
4217:
4210:
4177:
4173:
4166:
4141:
4137:
4130:
4111:
4105:
4078:
4074:
4064:
4029:
4023:
3988:
3982:
3955:
3951:
3941:
3908:
3904:
3898:
3861:
3857:
3847:
3812:
3808:
3798:
3773:
3769:
3763:
3738:
3735:Biochemistry
3734:
3728:
3693:
3689:
3679:
3644:
3640:
3630:
3595:
3591:
3581:
3546:
3542:
3532:
3507:
3503:
3497:
3472:
3468:
3462:
3425:
3421:
3411:
3378:
3374:
3360:
3319:
3315:
3308:
3281:
3277:
3267:
3232:
3228:
3218:
3185:
3181:
3175:
3138:
3134:
3124:
3089:
3085:
3075:
3038:
3034:
3024:
2991:
2987:
2981:
2930:
2926:
2920:
2887:
2883:
2876:
2841:
2837:
2827:
2782:
2778:
2768:
2741:
2737:
2727:
2682:
2678:
2668:
2658:
2651:
2626:
2622:
2616:
2583:
2579:
2569:
2545:10.1038/1565
2536:
2532:
2526:
2491:
2487:
2449:
2445:
2397:
2393:
2345:
2341:
2331:
2322:
2318:
2312:
2275:
2271:
2223:
2219:
2209:
2174:
2170:
2160:
2117:
2113:
2103:
2068:
2064:
2054:
2011:
2007:
1997:
1962:
1958:
1948:
1911:
1907:
1897:
1881:10.2741/S339
1872:
1868:
1862:
1827:
1823:
1813:
1778:
1774:
1764:
1729:
1725:
1715:
1680:
1677:Neuroscience
1676:
1666:
1631:
1627:
1617:
1592:
1589:Biochemistry
1588:
1582:
1547:
1543:
1533:
1501:(1): 18–25.
1498:
1494:
1484:
1459:
1455:
1449:
1419:(1): 81–88.
1416:
1412:
1405:
1389:(2): 48–52.
1386:
1382:
1372:
1347:
1343:
1337:
1300:
1297:BMC Genomics
1296:
1286:
1251:
1247:
1237:
1205:(1): 14–19.
1202:
1198:
1188:
1155:
1151:
1145:
1108:
1105:PLOS Biology
1104:
1094:
1049:
1045:
1035:
1010:
1006:
993:
958:
954:
906:
891:
885:
874:
870:white matter
855:
835:
792:gantenerumab
784:bapineuzumab
773:
758:
726:
710:
691:
636:glycoprotein
622:
610:Adults with
609:
580:
564:
559:pathogenesis
552:
544:
533:
516:protein fold
489:
476:
472:inflammatory
449:
431:
377:
373:
370:Amyloid beta
369:
368:
326:
245:Alt. symbols
18:
4646:Amyloidosis
4344:Amyloidosis
3864:(5): 1068.
2325:(1): 51–56.
2226:(1): 1–10.
800:solanezumab
698:proteolytic
652:γ-secretase
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