View source for Amyloid beta

{{Short description|Group of peptides}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox protein family
| Symbol = APP
| Name = Amyloid beta peptide (beta-APP)
| image = Abeta 2lfm.jpg
| width =
| caption = A partially folded structure of amyloid beta(1 40) in an aqueous environment (pdb 2lfm)<ref name="Vivekanandan_2011"/>
| Pfam = PF03494
| Pfam_clan = 
| InterPro = IPR013803
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 2lfm
| TCDB = 1.C.50
| OPM family = 304
| OPM protein = 2y3k
| CAZy =
| CDD =
| Membranome superfamily= 45
}}
{{infobox protein
| Name = amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)
| caption = Processing of the amyloid precursor protein
| image = APP_processing.png
| width = 300
| HGNCid = 620
| Symbol = [[Amyloid precursor protein|APP]]
| AltSymbols = AD1
| EntrezGene = 351
| OMIM = 104760
| RefSeq = NM_000484
| UniProt = P05067
<!-- | Ensembl = ENSG00000142192 -->
| PDB =
| ECnumber =
| Chromosome = 21
| Arm = q
| Band = 21.2
| LocusSupplementaryData =
}}
'''Amyloid beta''' ('''Aβ''', '''Abeta''' or '''beta-amyloid''') denotes [[peptide]]s of 36–43 [[amino acid]]s that are the main component of the [[amyloid plaques]] found in the brains of people with [[Alzheimer's disease]].<ref name="pmid22813427">{{cite journal | vauthors = Hamley IW | title = The amyloid beta peptide: a chemist's perspective. Role in Alzheimer's and fibrillization | journal = Chemical Reviews | volume = 112 | issue = 10 | pages = 5147–5192 | date = October 2012 | pmid = 22813427 | doi = 10.1021/cr3000994 | url = https://centaur.reading.ac.uk/30230/2/AbetaRevisednew%20-IWH%20%281%29.pdf }}</ref> The peptides derive from the [[amyloid-beta precursor protein]] (APP), which is cleaved by [[Beta-secretase 1|beta secretase]] and [[gamma secretase]] to yield Aβ in a cholesterol-dependent process and [[substrate presentation]].<ref>{{cite journal | vauthors = Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB | title = Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 118 | issue = 33 | pages = e2102191118 | date = August 2021 | pmid = 34385305 | pmc = 8379952 | doi = 10.1073/pnas.2102191118 | doi-access = free | bibcode = 2021PNAS..11802191W }}</ref> Both neurons and oligodendrocytes produce and release Aβ in the brain, contributing to formation of amyloid plaques.<ref>{{cite journal | vauthors = Rajani RM, Ellingford R, Hellmuth M, Harris SS, Taso OS, Graykowski D, Lam FK, Arber C, Fertan E, Danial JS, Swire M, Lloyd M, Giovannucci TA, Bourdenx M, Klenerman D, Vassar R, Wray S, Sala Frigerio C, Busche MA | title = Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease | journal = PLOS Biology | volume = 22 | issue = 7 | pages = e3002727 | date = July 2024 | pmid = 39042667 | pmc = 11265669 | doi = 10.1371/journal.pbio.3002727 | doi-access = free }}</ref> Aβ molecules can aggregate to form flexible soluble [[oligomer]]s 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 [[prion]] infection. The oligomers are toxic to [[nerve cell]]s.<ref>{{cite journal | vauthors = Haass C, Selkoe DJ | title = Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 2 | pages = 101–112 | date = February 2007 | pmid = 17245412 | doi = 10.1038/nrm2101 | s2cid = 32991755 }}</ref> The other protein implicated in Alzheimer's disease, [[tau protein]], also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.<ref>{{cite journal | vauthors = Nussbaum JM, Seward ME, Bloom GS | title = Alzheimer disease: a tale of two prions | journal = Prion | volume = 7 | issue = 1 | pages = 14–19 | date = Jan–Feb 2013 | pmid = 22965142 | pmc = 3609044 | doi = 10.4161/pri.22118 }}</ref><ref>{{cite journal | vauthors = Pulawski W, Ghoshdastider U, Andrisano V, Filipek S | title = Ubiquitous amyloids | journal = Applied Biochemistry and Biotechnology | volume = 166 | issue = 7 | pages = 1626–1643 | date = April 2012 | pmid = 22350870 | pmc = 3324686 | doi = 10.1007/s12010-012-9549-3 }}</ref>

A study has suggested that APP and its amyloid potential is of ancient origins, dating as far back as early [[deuterostomes]].<ref name="Sarkar">{{cite journal | vauthors = Tharp WG, Sarkar IN | title = Origins of amyloid-β | journal = BMC Genomics | volume = 14 | issue = 1 | pages = 290 | date = April 2013 | pmid = 23627794 | pmc = 3660159 | doi = 10.1186/1471-2164-14-290 | doi-access = free }}</ref>

== Normal function ==
{{See also|Amyloid precursor protein#Biological function}}
The normal function of Aβ is not yet known.<ref name="pmid19584429">{{cite journal | vauthors = Hiltunen M, van Groen T, Jolkkonen J | title = Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: evidence from experimental studies | journal = Journal of Alzheimer's Disease | volume = 18 | issue = 2 | pages = 401–412 | year = 2009 | pmid = 19584429 | doi = 10.3233/JAD-2009-1154 }}</ref>   Though some animal studies have shown that the absence of Aβ does not lead to any obvious loss of physiological function,<ref>{{cite journal | vauthors = Sadigh-Eteghad S, Talebi M, Farhoudi M, EJ Golzari S, Sabermarouf B, Mahmoudi J | title = Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner|journal=Journal of Medical Hypotheses and Ideas| year =2014 | volume = 8 | issue = 2| pages = 48–52 | doi = 10.1016/j.jmhi.2014.01.001 | doi-access = free }}</ref><ref name="pmid13678669">{{cite journal | vauthors = Luo Y, Bolon B, Damore MA, Fitzpatrick D, Liu H, Zhang J, Yan Q, Vassar R, Citron M | title = BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time | journal = Neurobiology of Disease | volume = 14 | issue = 1 | pages = 81–88 | date = October 2003 | pmid = 13678669 | doi = 10.1016/S0969-9961(03)00104-9 | s2cid = 8367440 }}</ref> several potential activities have been discovered for Aβ, including activation of [[kinase]] [[enzyme]]s,<ref name="pmid15023353">{{cite journal | vauthors = Bogoyevitch MA, Boehm I, Oakley A, Ketterman AJ, Barr RK | title = Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1697 | issue = 1–2 | pages = 89–101 | date = March 2004 | pmid = 15023353 | doi = 10.1016/j.bbapap.2003.11.016 }}</ref><ref name="pmid19747481">{{cite journal | vauthors = Tabaton M, Zhu X, Perry G, Smith MA, Giliberto L | title = Signaling effect of amyloid-beta(42) on the processing of AbetaPP | journal = Experimental Neurology | volume = 221 | issue = 1 | pages = 18–25 | date = January 2010 | pmid = 19747481 | pmc = 2812589 | doi = 10.1016/j.expneurol.2009.09.002 }}</ref> protection against [[oxidative stress]],<ref name="pmid12077180">{{cite journal | vauthors = Zou K, Gong JS, Yanagisawa K, Michikawa M | title = A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage | journal = The Journal of Neuroscience | volume = 22 | issue = 12 | pages = 4833–4841 | date = June 2002 | pmid = 12077180 | pmc = 6757724 | doi = 10.1523/JNEUROSCI.22-12-04833.2002 }}</ref><ref name="pmid19320465">{{cite journal | vauthors = Baruch-Suchodolsky R, Fischer B | title = Abeta40, either soluble or aggregated, is a remarkably potent antioxidant in cell-free oxidative systems | journal = Biochemistry | volume = 48 | issue = 20 | pages = 4354–4370 | date = May 2009 | pmid = 19320465 | doi = 10.1021/bi802361k }}</ref> regulation of [[cholesterol]] transport,<ref name="pmid12206998">{{cite journal | vauthors = Yao ZX, Papadopoulos V | title = Function of beta-amyloid in cholesterol transport: a lead to neurotoxicity | journal = FASEB Journal | volume = 16 | issue = 12 | pages = 1677–1679 | date = October 2002 | pmid = 12206998 | doi = 10.1096/fj.02-0285fje | s2cid = 17813857 | doi-access = free }}</ref><ref name="pmid19401218">{{cite journal | vauthors = Igbavboa U, Sun GY, Weisman GA, He Y, Wood WG | title = Amyloid beta-protein stimulates trafficking of cholesterol and caveolin-1 from the plasma membrane to the Golgi complex in mouse primary astrocytes | journal = Neuroscience | volume = 162 | issue = 2 | pages = 328–338 | date = August 2009 | pmid = 19401218 | pmc = 3083247 | doi = 10.1016/j.neuroscience.2009.04.049 }}</ref> functioning as a [[transcription factor]],<ref name="pmid21699964">{{cite journal | vauthors = Maloney B, Lahiri DK | title = 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 | journal = Gene | volume = 488 | issue = 1–2 | pages = 1–12 | date = November 2011 | pmid = 21699964 | pmc = 3381326 | doi = 10.1016/j.gene.2011.06.004 }}</ref><ref name="pmid21708232">{{cite journal | vauthors = Bailey JA, Maloney B, Ge YW, Lahiri DK | title = 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 | journal = Gene | volume = 488 | issue = 1–2 | pages = 13–22 | date = November 2011 | pmid = 21708232 | pmc = 3372404 | doi = 10.1016/j.gene.2011.06.017 }}</ref> and anti-microbial activity (potentially associated with Aβ's pro-[[Inflammation|inflammatory]] activity).<ref name="pmid22081976">{{cite journal | vauthors = Kagan BL, Jang H, Capone R, Teran Arce F, Ramachandran S, Lal R, Nussinov R | title = Antimicrobial properties of amyloid peptides | journal = Molecular Pharmaceutics | volume = 9 | issue = 4 | pages = 708–717 | date = April 2012 | pmid = 22081976 | pmc = 3297685 | doi = 10.1021/mp200419b }}</ref><ref name="pmid22652879">{{cite journal | vauthors = Schluesener HJ, Su Y, Ebrahimi A, Pouladsaz D | title = Antimicrobial peptides in the brain: neuropeptides and amyloid | journal = Frontiers in Bioscience | volume = 4 | issue = 4 | pages = 1375–1380 | date = June 2012 | pmid = 22652879 | doi = 10.2741/S339 }}</ref><ref name="pmid30603085">{{cite journal | vauthors = Li H, Liu CC, Zheng H, Huang TY | title = Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer's disease -conformist, nonconformist, and realistic prospects for AD pathogenesis | journal = Translational Neurodegeneration | volume = 7 | pages = 34 | date = 2018 | pmid = 30603085 | pmc = 6306008 | doi = 10.1186/s40035-018-0139-3 | doi-access = free }}</ref>

The [[glymphatic system]] clears metabolic waste from the mammalian brain, and in particular amyloid beta.<ref name="pmid22896675">{{cite journal | vauthors = Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M | title = A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β | journal = Science Translational Medicine | volume = 4 | issue = 147 | pages = 147ra111 | date = August 2012 | pmid = 22896675 | pmc = 3551275 | doi = 10.1126/scitranslmed.3003748 }}</ref> 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<ref>{{cite journal | vauthors = Shen Y, Joachimiak A, Rosner MR, Tang WJ | title = Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism | journal = Nature | volume = 443 | issue = 7113 | pages = 870–874 | date = October 2006 | pmid = 17051221 | pmc = 3366509 | doi = 10.1038/nature05143 | bibcode = 2006Natur.443..870S }}</ref> and presequence protease.<ref>{{cite journal | vauthors = King JV, Liang WG, Scherpelz KP, Schilling AB, Meredith SC, Tang WJ | title = Molecular basis of substrate recognition and degradation by human presequence protease | journal = Structure | volume = 22 | issue = 7 | pages = 996–1007 | date = July 2014 | pmid = 24931469 | pmc = 4128088 | doi = 10.1016/j.str.2014.05.003 }}</ref> The rate of removal is significantly increased during sleep.<ref>{{cite journal | vauthors = Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M | title = Sleep drives metabolite clearance from the adult brain | journal = Science | volume = 342 | issue = 6156 | pages = 373–377 | date = October 2013 | pmid = 24136970 | pmc = 3880190 | doi = 10.1126/science.1241224 | bibcode = 2013Sci...342..373X }}</ref> However, the significance of the glymphatic system in Aβ clearance in Alzheimer's disease is unknown.<ref>{{cite journal | vauthors = Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, Axel L, Rusinek H, Nicholson C, Zlokovic BV, Frangione B, Blennow K, Ménard J, Zetterberg H, Wisniewski T, de Leon MJ | title = Clearance systems in the brain-implications for Alzheimer disease | journal = Nature Reviews. Neurology | volume = 11 | issue = 8 | pages = 457–470 | date = August 2015 | pmid = 26195256 | pmc = 4694579 | doi = 10.1038/nrneurol.2015.119 }}</ref>

== Intervention strategies ==
Aβ is the main component of [[amyloid plaque]]s, extracellular deposits found in the [[brain]]s of people with Alzheimer's disease.<ref>{{cite journal | vauthors = Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J | title = Amyloid-beta: a crucial factor in Alzheimer's disease | journal = Medical Principles and Practice | volume = 24 | issue = 1 | pages = 1–10 | year = 2014 | pmid = 25471398 | pmc = 5588216 | doi = 10.1159/000369101 }}</ref> Aβ can also form the deposits that line [[cerebral blood vessel]]s in [[cerebral amyloid angiopathy]]. The plaques are composed of a tangle of Aβ [[Protein oligomer|oligomers]]{{bsn|date=June 2025}}<ref name="pmid33308303">{{cite journal | vauthors = Röhr D, Boon BD, Schuler M, Kremer K, Hoozemans JJ, Bouwman FH, El-Mashtoly SF, Nabers A, Großerueschkamp F, Rozemuller AJ, Gerwert K | title = Label-free vibrational imaging of different Aβ plaque types in Alzheimer's disease reveals sequential events in plaque development | journal = Acta Neuropathologica Communications | volume = 8 | issue = 1 | pages = 222 | date = December 2020 | pmid = 33308303 | pmc = 7733282 | doi = 10.1186/s40478-020-01091-5 | doi-access = free }}</ref> and regularly ordered aggregates called [[Amyloid#Structure|amyloid fibrils]],<ref>{{cite journal |vauthors=Parker MH, Reitz AB |title=Assembly of β-Amyloid Aggregates at the Molecular Level |journal=Chemtracts-Organic Chemistry |year=2000 |volume=13 |issue=1 |pages=51–56}}</ref> a [[protein folding|protein fold]] shared by other peptides such as the [[prion]]s associated with protein misfolding disease, also known as [[proteinopathy]].{{cn|date=January 2025}}

===Alzheimer's disease===
Research suggests that soluble oligomeric forms of the amyloid beta may be causative agents in the development of [[Alzheimer's disease]].<ref name="pmid18568035">{{cite journal | vauthors = Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ | title = Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory | journal = Nature Medicine | volume = 14 | issue = 8 | pages = 837–842 | date = August 2008 | pmid = 18568035 | pmc = 2772133 | doi = 10.1038/nm1782 }}</ref> It is generally believed that Aβ oligomers are the most toxic.<ref name="pmid22837695">{{cite journal | vauthors = Zhao LN, Long HW, Mu Y, Chew LY | title = The toxicity of amyloid β oligomers | journal = International Journal of Molecular Sciences | volume = 13 | issue = 6 | pages = 7303–7327 | year = 2012 | pmid = 22837695 | pmc = 3397527 | doi = 10.3390/ijms13067303 | doi-access = free }}</ref> Several genetic, cell biology, biochemical and animal studies using [[Experimental models of Alzheimer's disease|experimental models]] support the concept that Aβ plays a central role in the development of Alzheimer's disease pathology.<ref name="Ghiso_2002">{{cite journal | vauthors = Ghiso J, Frangione B | title = Amyloidosis and Alzheimer's disease | journal = Advanced Drug Delivery Reviews | volume = 54 | issue = 12 | pages = 1539–1551 | date = December 2002 | pmid = 12453671 | doi = 10.1016/S0169-409X(02)00149-7 }}</ref><ref name="Selkoe_2001">{{cite journal | vauthors = Selkoe DJ | title = Clearing the brain's amyloid cobwebs | journal = Neuron | volume = 32 | issue = 2 | pages = 177–180 | date = October 2001 | pmid = 11683988 | doi = 10.1016/S0896-6273(01)00475-5 | s2cid = 17860343 | doi-access = free }}</ref>

Brain Aβ is elevated in people with sporadic Alzheimer's disease. Aβ is the main constituent of brain [[parenchymal]] and vascular amyloid; it contributes to cerebrovascular lesions and is neurotoxic.<ref name="Ghiso_2002"/><ref name="Selkoe_2001"/><ref name="pmid10196523">{{cite journal | vauthors = Hardy J, Duff K, Hardy KG, Perez-Tur J, Hutton M | title = Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau | journal = Nature Neuroscience | volume = 1 | issue = 5 | pages = 355–358 | date = September 1998 | pmid = 10196523 | doi = 10.1038/1565 | s2cid = 52807658 }}</ref> 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 proteolytic enzymes gamma- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein).<ref name="pmid10531052">{{cite journal | vauthors = Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M | title = Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE | journal = Science | volume = 286 | issue = 5440 | pages = 735–741 | date = October 1999 | pmid = 10531052 | doi = 10.1126/science.286.5440.735 | s2cid = 42481897 | url = https://escholarship.org/uc/item/1kf9n6tq }}</ref><ref name="pmid12453676">{{cite journal | vauthors = Vassar R | title = Beta-secretase (BACE) as a drug target for Alzheimer's disease | journal = Advanced Drug Delivery Reviews | volume = 54 | issue = 12 | pages = 1589–1602 | date = December 2002 | pmid = 12453676 | doi = 10.1016/S0169-409X(02)00157-6 }}</ref> Aβ circulates in plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) mainly as soluble Aβ40.<ref name="Ghiso_2002"/><ref>{{cite book |vauthors=Zlokovic BV, Frangione B |title=Transport-clearance hypothesis for Alzheimer's disease and potential therapeutic implications |year=2003 |publisher=Landes Bioscience |pages=114–122 |url=https://www.ncbi.nlm.nih.gov/books/NBK5975/}}</ref>  Amyloid plaques contain both Aβ40 and Aβ42,<ref name="pmid3159021">{{cite journal | vauthors = Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K | title = Amyloid plaque core protein in Alzheimer disease and Down syndrome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 12 | pages = 4245–4249 | date = June 1985 | pmid = 3159021 | pmc = 397973 | doi = 10.1073/pnas.82.12.4245 | doi-access = free | bibcode = 1985PNAS...82.4245M }}</ref> while vascular amyloid is predominantly the shorter Aβ40. Several sequences of Aβ were found in both lesions.<ref name="pmid8943274">{{cite journal | vauthors = Castaño EM, Prelli F, Soto C, Beavis R, Matsubara E, Shoji M, Frangione B | title = 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 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 50 | pages = 32185–32191 | date = December 1996 | pmid = 8943274 | doi = 10.1074/jbc.271.50.32185 | doi-access = free }}</ref><ref name="pmid8248178">{{cite journal | vauthors = Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, Ball MJ | title = beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 22 | pages = 10836–10840 | date = November 1993 | pmid = 8248178 | pmc = 47873 | doi = 10.1073/pnas.90.22.10836 | doi-access = free | bibcode = 1993PNAS...9010836R }}</ref>

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 [[neurite|neuritic]] plaques)<ref name="pmid10487842">{{cite journal | vauthors = Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J | title = Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease | journal = The American Journal of Pathology | volume = 155 | issue = 3 | pages = 853–862 | date = September 1999 | pmid = 10487842 | pmc = 1866907 | doi = 10.1016/S0002-9440(10)65184-X }}</ref> have been implicated in the [[etiology|pathogenesis]] 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.<ref name="pm17056725">{{cite journal | vauthors = Bu Z, Shi Y, Callaway DJ, Tycko R | title = Molecular alignment within β-sheets in Aβ<sub>14-23</sub> fibrils: solid-state NMR experiments and theoretical predictions | journal = Biophysical Journal | volume = 92 | issue = 2 | pages = 594–602 | date = January 2007 | pmid = 17056725 | pmc = 1751388 | doi = 10.1529/biophysj.106.091017 | bibcode = 2007BpJ....92..594B | url = }}</ref> One study further correlated Aβ42 levels 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.<ref>{{cite journal | vauthors = Schirinzi T, Di Lazzaro G, Sancesario GM, Colona VL, Scaricamazza E, Mercuri NB, Martorana A, Sancesario G | title = Levels of amyloid-beta-42 and CSF pressure are directly related in patients with Alzheimer's disease | journal = Journal of Neural Transmission | volume = 124 | issue = 12 | pages = 1621–1625 | date = December 2017 | pmid = 28866757 | doi = 10.1007/s00702-017-1786-8 | s2cid = 22267507 }}</ref>

The "[[amyloid hypothesis]]" {{emdash}} that the plaques are responsible for the pathology of Alzheimer's disease {{emdash}} is accepted by the majority of researchers, but is not conclusively established. An alternative hypothesis is that amyloid [[oligomer]]s rather than plaques are responsible for the disease.<ref name="pmid22837695"/><ref name="pmid12702875">{{cite journal | vauthors = Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG | title = Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis | journal = Science | volume = 300 | issue = 5618 | pages = 486–489 | date = April 2003 | pmid = 12702875 | doi = 10.1126/science.1079469 | hdl-access = free | s2cid = 29614957 | bibcode = 2003Sci...300..486K | hdl = 2027.42/150615 }}</ref> This more recent variation of the amyloid hypothesis identifies the cytotoxic species as an intermediate misfolded form of amyloid beta, neither a soluble monomer nor a mature aggregated polymer but an [[oligomer]]ic species. This [[Ion channel hypothesis of Alzheimer's disease|ion channel hypothesis]] postulates that oligomers of soluble, non-fibrillar Aβ form membrane ion channels allowing unregulated calcium influx into neurons.<ref>{{cite journal |vauthors=Arispe N, Rojas E, Pollard HB |date=January 1993 |title=Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=90 |issue=2 |pages=567–71 |bibcode=1993PNAS...90..567A |doi=10.1073/pnas.90.2.567 |pmc=45704 |pmid=8380642 |doi-access=free}}</ref>

[[File:Apomorphine therapeutic scheme.png|thumb|325px|Flow chart depicting the role of [[Apomorphine#Alzheimer's disease|apomorphine]] in Alzheimer's disease.]]

This cytotoxic-fibril hypothesis presents a clear target for drug development: inhibit the fibrillization process. Much early development work on [[lead compound]]s has focused on this inhibition;<ref name="Blanchard2">{{cite journal |vauthors=Blanchard BJ, Chen A, Rozeboom LM, Stafford KA, Weigele P, Ingram VM |date=October 2004 |title=Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=101 |issue=40 |pages=14326–32 |bibcode=2004PNAS..10114326B |doi=10.1073/pnas.0405941101 |pmc=521943 |pmid=15388848 |doi-access=free}}</ref><ref name="Porat">{{cite journal |vauthors=Porat Y, Abramowitz A, Gazit E |date=January 2006 |title=Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism |journal=Chemical Biology & Drug Design |volume=67 |issue=1 |pages=27–37 |doi=10.1111/j.1747-0285.2005.00318.x |pmid=16492146 |doi-access=free}}</ref><ref name="Kanapathipillai">{{cite journal |vauthors=Kanapathipillai M, Lentzen G, Sierks M, Park CB |date=August 2005 |title=Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer's beta-amyloid |journal=FEBS Letters |volume=579 |issue=21 |pages=4775–80 |doi=10.1016/j.febslet.2005.07.057 |pmid=16098972 |doi-access=free|bibcode=2005FEBSL.579.4775K }}</ref> most are also reported to reduce neurotoxicity, but the toxic-oligomer theory suggests that prevention of oligomeric assembly is more important <ref name="ReferenceA">{{cite journal |vauthors=Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, Motomura K, Soejima N, Yamasaki R, Hashimoto T, Tabira T, LaFerla FM, Kira J |date=February 2011 |title=Apomorphine treatment in Alzheimer mice promoting amyloid-β degradation |journal=Annals of Neurology |volume=69 |issue=2 |pages=248–56 |doi=10.1002/ana.22319 |pmid=21387370 |s2cid=242138}}</ref><ref name="lashuel">{{cite journal |vauthors=Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJ |date=November 2002 |title=New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease |journal=The Journal of Biological Chemistry |volume=277 |issue=45 |pages=42881–90 |doi=10.1074/jbc.M206593200 |pmid=12167652 |doi-access=free}}</ref>
For example, [[apomorphine]] was seen to significantly improve memory function through the increased successful completion of the [[Morris water navigation task|Morris Water Maze]].<ref name="ReferenceA" />

=== Cancer ===
While Aβ has been implicated in [[cancer]] 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 [[Esophageal cancer|esophageal]], [[Colorectal cancer|colorectal]], [[Lung cancer|lung]], and [[Hepatic cancer|hepatic]], in response to observed reductions in risk for developing Alzheimer's disease in survivors of these cancers.{{cn|date=February 2025}} All cancers were shown to be associated positively with increased Aβ levels, particularly hepatic cancers.<ref>{{cite journal | vauthors = Jin WS, Bu XL, Liu YH, Shen LL, Zhuang ZQ, Jiao SS, Zhu C, Wang QH, Zhou HD, Zhang T, Wang YJ | title = Plasma Amyloid-Beta Levels in Patients with Different Types of Cancer | journal = Neurotoxicity Research | volume = 31 | issue = 2 | pages = 283–288 | date = February 2017 | pmid = 27913965 | doi = 10.1007/s12640-016-9682-9 | s2cid = 3795042 }}</ref> 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.<ref>{{cite journal | vauthors = Lim S, Yoo BK, Kim HS, Gilmore HL, Lee Y, Lee HP, Kim SJ, Letterio J, Lee HG | title = Amyloid-β precursor protein promotes cell proliferation and motility of advanced breast cancer | journal = BMC Cancer | volume = 14 | pages = 928 | date = December 2014 | pmid = 25491510 | pmc = 4295427 | doi = 10.1186/1471-2407-14-928 | doi-access = free }}</ref>

=== Down syndrome ===
Adults with [[Down syndrome]] 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.<ref name=":0">{{cite journal | vauthors = Hartley SL, Handen BL, Devenny D, Mihaila I, Hardison R, Lao PJ, Klunk WE, Bulova P, Johnson SC, Christian BT | title = Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome | journal = Neurobiology of Aging | volume = 58 | pages = 68–76 | date = October 2017 | pmid = 28715661 | pmc = 5581712 | doi = 10.1016/j.neurobiolaging.2017.05.019 }}</ref>

== Formation ==

Aβ is  formed after sequential [[peptidase|cleavage]] of the [[amyloid precursor protein]] (APP), a [[transmembrane protein|transmembrane]] [[glycoprotein]] of undetermined function. APP can be cleaved by the [[proteolysis|proteolytic]] enzymes [[alpha secretase|α-]], [[BACE|β-]] and [[gamma secretase|γ-secretase]]; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the [[C-terminus|C-terminal]] end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 30–51 [[amino acid]] residues in length.<ref name="pmid24225948">{{cite journal | vauthors = Olsson F, Schmidt S, Althoff V, Munter LM, Jin S, Rosqvist S, Lendahl U, Multhaup G, Lundkvist J | title = Characterization of intermediate steps in amyloid beta (Aβ) production under near-native conditions | journal = The Journal of Biological Chemistry | volume = 289 | issue = 3 | pages = 1540–1550 | date = January 2014 | pmid = 24225948 | pmc = 3894335 | doi = 10.1074/jbc.M113.498246 | doi-access = free }}</ref> The most common isoforms are Aβ<sub>40</sub> and Aβ<sub>42</sub>; the longer form is typically produced by cleavage that occurs in the [[endoplasmic reticulum]], while the shorter form is produced by cleavage in the trans-[[Golgi apparatus|Golgi]] network.<ref name="pmid9288729">{{cite journal | vauthors = Hartmann T, Bieger SC, Brühl B, Tienari PJ, Ida N, Allsop D, Roberts GW, Masters CL, Dotti CG, Unsicker K, Beyreuther K | title = Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides | journal = Nature Medicine | volume = 3 | issue = 9 | pages = 1016–1020 | date = September 1997 | pmid = 9288729 | doi = 10.1038/nm0997-1016 | s2cid = 8390460 }}</ref>

== Genetics ==
{{See also|Amyloid precursor protein}}
Autosomal-dominant mutations in APP cause hereditary [[familial Alzheimer disease|early-onset Alzheimer's disease]] (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.<ref name="pmid18631956">{{cite journal | title = 2008 Alzheimer's disease facts and figures | journal = Alzheimer's & Dementia | volume = 4 | issue = 2 | pages = 110–133 | date = March 2008 | pmid = 18631956 | doi = 10.1016/j.jalz.2008.02.005 | s2cid = 43750218 | doi-access = free | author1 = Alzheimer's Association }}</ref> However, familial Alzheimer's disease is likely to result from altered [[Proteolysis|proteolytic]] processing. This is evidenced by the fact that many mutations that lead to fAD occur near γ-secretase cleavage sites on APP.<ref>{{cite journal | vauthors = De Jonghe C, Esselens C, Kumar-Singh S, Craessaerts K, Serneels S, Checler F, Annaert W, Van Broeckhoven C, De Strooper B | title = Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect Abeta secretion and APP C-terminal fragment stability | journal = Human Molecular Genetics | volume = 10 | issue = 16 | pages = 1665–1671 | date = August 2001 | pmid = 11487570 | doi = 10.1093/hmg/10.16.1665 | doi-access = free }}</ref> One of the most common mutations causing fAD, [[Early-onset Alzheimer's disease#APP – amyloid beta (A4) precursor protein|London Mutation]], occurs at codon 717 of the APP gene,<ref>{{cite journal | vauthors = Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J | title = Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene | journal = Nature | volume = 353 | issue = 6347 | pages = 844–846 | date = October 1991 | pmid = 1944558 | doi = 10.1038/353844a0 | s2cid = 4345311 | bibcode = 1991Natur.353..844C }}</ref><ref>{{cite journal | vauthors = Lantos PL, Luthert PJ, Hanger D, Anderton BH, Mullan M, Rossor M | title = Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology | journal = Neuroscience Letters | volume = 137 | issue = 2 | pages = 221–224 | date = March 1992 | pmid = 1584463 | doi = 10.1016/0304-3940(92)90408-y | s2cid = 25383047 | author6-link = Martin Rossor | author5-link = Michael Mullan }}</ref> 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 [[cerebral amyloid angiopathy]] (CAA).<ref>{{cite journal | vauthors = Lloyd GM, Trejo-Lopez JA, Xia Y, McFarland KN, Lincoln SJ, Ertekin-Taner N, Giasson BI, Yachnis AT, Prokop S | title = Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier - phenotypic variability in autosomal dominant Alzheimer's disease | journal = Acta Neuropathologica Communications | volume = 8 | issue = 1 | pages = 31 | date = March 2020 | pmid = 32164763 | pmc = 7068954 | doi = 10.1186/s40478-020-0891-3 | doi-access = free }}</ref>

The gene for the amyloid precursor protein is located on [[chromosome 21 (human)|chromosome 21]], and accordingly people with [[Down syndrome]] have a very high incidence of Alzheimer's disease.<ref>{{cite journal | vauthors = Glenner GG, Wong CW | title = Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein | journal = Biochemical and Biophysical Research Communications | volume = 122 | issue = 3 | pages = 1131–1135 | date = August 1984 | pmid = 6236805 | doi = 10.1016/0006-291X(84)91209-9 }}</ref>

== Structure and toxicity ==

Amyloid beta is commonly thought to be [[intrinsically unstructured protein|intrinsically unstructured]], meaning that in solution it does not acquire a unique tertiary [[protein folding|fold]] but rather populates a set of structures. As such, it cannot be crystallized and most structural knowledge on amyloid beta comes from [[NMR]] and [[molecular dynamics]]. Early NMR-derived models of a 26-aminoacid polypeptide from amyloid beta (Aβ 10–35) show a collapsed [[random coil|coil]] structure devoid of significant [[secondary structure]] content.<ref name="zhang2000">{{cite journal | vauthors = Zhang S, Iwata K, Lachenmann MJ, Peng JW, Li S, Stimson ER, Lu Y, Felix AM, Maggio JE, Lee JP | title = The Alzheimer's peptide a beta adopts a collapsed coil structure in water | journal = Journal of Structural Biology | volume = 130 | issue = 2–3 | pages = 130–141 | date = June 2000 | pmid = 10940221 | doi = 10.1006/jsbi.2000.4288 }}</ref> However, the most recent (2012) NMR structure of (Aβ 1-40) has significant secondary and tertiary structure.<ref name="Vivekanandan_2011">{{cite journal | vauthors = Vivekanandan S, Brender JR, Lee SY, Ramamoorthy A | title = A partially folded structure of amyloid-beta(1-40) in an aqueous environment | journal = Biochemical and Biophysical Research Communications | volume = 411 | issue = 2 | pages = 312–316 | date = July 2011 | pmid = 21726530 | pmc = 3148408 | doi = 10.1016/j.bbrc.2011.06.133 }}</ref> [[Replica exchange]] molecular dynamics studies suggested that amyloid beta can indeed populate multiple discrete structural states;<ref name="yang2008">{{cite journal | vauthors = Yang M, Teplow DB | title = Amyloid beta-protein monomer folding: free-energy surfaces reveal alloform-specific differences | journal = Journal of Molecular Biology | volume = 384 | issue = 2 | pages = 450–464 | date = December 2008 | pmid = 18835397 | pmc = 2673916 | doi = 10.1016/j.jmb.2008.09.039 }}</ref> more recent studies identified a multiplicity of discrete conformational clusters by statistical analysis.<ref name="sgourakis2010">{{cite journal | vauthors = Sgourakis NG, Merced-Serrano M, Boutsidis C, Drineas P, Du Z, Wang C, Garcia AE | title = Atomic-level characterization of the ensemble of the Aβ(1-42) monomer in water using unbiased molecular dynamics simulations and spectral algorithms | journal = Journal of Molecular Biology | volume = 405 | issue = 2 | pages = 570–583 | date = January 2011 | pmid = 21056574 | pmc = 3060569 | doi = 10.1016/j.jmb.2010.10.015 }}</ref> By NMR-guided simulations, amyloid beta 1-40 and amyloid beta 1-42 also seem to feature highly different conformational states,<ref name="sgourakis2007">{{cite journal | vauthors = Sgourakis NG, Yan Y, McCallum SA, Wang C, Garcia AE | title = The Alzheimer's peptides Abeta40 and 42 adopt distinct conformations in water: a combined MD / NMR study | journal = Journal of Molecular Biology | volume = 368 | issue = 5 | pages = 1448–1457 | date = May 2007 | pmid = 17397862 | pmc = 1978067 | doi = 10.1016/j.jmb.2007.02.093 }}</ref> with the C-terminus of amyloid beta 1-42 being more structured than that of the 1-40 fragment.

Low-temperature and low-salt conditions allowed to isolate pentameric disc-shaped oligomers devoid of beta structure.<ref name="ahmed2010">{{cite journal | vauthors = Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, Elliott JI, Van Nostrand WE, Smith SO | title = Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils | journal = Nature Structural & Molecular Biology | volume = 17 | issue = 5 | pages = 561–567 | date = May 2010 | pmid = 20383142 | pmc = 2922021 | doi = 10.1038/nsmb.1799 }}</ref> 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 fibrils;<ref name="yu2009">{{cite journal | vauthors = Yu L, Edalji R, Harlan JE, Holzman TF, Lopez AP, Labkovsky B, Hillen H, Barghorn S, Ebert U, Richardson PL, Miesbauer L, Solomon L, Bartley D, Walter K, Johnson RW, Hajduk PJ, Olejniczak ET | title = Structural characterization of a soluble amyloid beta-peptide oligomer | journal = Biochemistry | volume = 48 | issue = 9 | pages = 1870–1877 | date = March 2009 | pmid = 19216516 | doi = 10.1021/bi802046n }}</ref> computational studies suggest an antiparallel beta-turn-beta motif instead for membrane-embedded oligomers.<ref name="wales2010">{{cite journal | vauthors = Strodel B, Lee JW, Whittleston CS, Wales DJ | title = Transmembrane structures for Alzheimer's Aβ(1-42) oligomers | journal = Journal of the American Chemical Society | volume = 132 | issue = 38 | pages = 13300–13312 | date = September 2010 | pmid = 20822103 | doi = 10.1021/ja103725c }}</ref>

==Immunotherapy research==
{{further|Alzheimer's disease#Research directions}} <!-- large overlap -->
[[Immunotherapy]] 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 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 [[aducanumab]], [[bapineuzumab]], [[crenezumab]], [[gantenerumab]], [[lecanemab]], and [[solanezumab]].<ref name="Cummings_2017">{{cite journal | vauthors = Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K | title = Alzheimer's disease drug development pipeline: 2017 | journal = Alzheimer's & Dementia | volume = 3 | issue = 3 | pages = 367–384 | date = September 2017 | pmid = 29067343 | pmc = 5651419 | doi = 10.1016/j.trci.2017.05.002 | department = review }}</ref><ref name="Schilling_2018">{{cite journal | vauthors = Schilling S, Rahfeld JU, Lues I, Lemere CA | title = Passive Aβ Immunotherapy: Current Achievements and Future Perspectives | journal = Molecules | volume = 23 | issue = 5 | pages = 1068 | date = May 2018 | pmid = 29751505 | pmc = 6099643 | doi = 10.3390/molecules23051068 | doi-access = free | department = review }}</ref>

== Measuring amyloid beta ==
[[Image:Cerebral amyloid angiopathy -2b- amyloid beta - intermed mag - cropped.jpg|thumb|[[Micrograph]] showing amyloid beta (brown) in [[amyloid plaques]] of the [[cerebral cortex]] (upper left of image) and cerebral [[blood vessel]]s (right of image) with [[immunostain]]ing]]

Imaging compounds, notably [[Pittsburgh compound B]], (6-OH-BTA-1, a [[thioflavin]]), can selectively bind to amyloid beta in vitro and in vivo. This technique, combined with [[Positron emission tomography|PET]] imaging, is used to image areas of plaque deposits in those with Alzheimer's.<ref>{{cite journal | vauthors = Heurling K, Leuzy A, Zimmer ER, Lubberink M, Nordberg A | title = Imaging β-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis | journal = European Journal of Nuclear Medicine and Molecular Imaging | volume = 43 | issue = 2 | pages = 362–373 | date = February 2016 | pmid = 26440450 | doi = 10.1007/s00259-015-3208-1 | s2cid = 2695342 }}</ref>

===Post mortem or in tissue biopsies===
Amyloid beta can be measured semiquantitatively with [[immunostain]]ing, which also allows one to determine location.  Amyloid beta may be primarily vascular, as in [[cerebral amyloid angiopathy]], or in [[amyloid plaques]] in [[white matter]].<ref>{{cite journal | vauthors = Ito H, Shimada H, Shinotoh H, Takano H, Sasaki T, Nogami T, Suzuki M, Nagashima T, Takahata K, Seki C, Kodaka F, Eguchi Y, Fujiwara H, Kimura Y, Hirano S, Ikoma Y, Higuchi M, Kawamura K, Fukumura T, Böö ÉL, Farde L, Suhara T | title = Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184 | journal = Journal of Nuclear Medicine | volume = 55 | issue = 6 | pages = 932–938 | date = June 2014 | pmid = 24732152 | doi = 10.2967/jnumed.113.133793 | doi-access = free }}</ref>

One sensitive method is [[ELISA]] which is an immunosorbent assay which utilizes a pair of [[antibodies]] that recognize amyloid beta.<ref name="pmid22528111">{{cite book | vauthors = Schmidt SD, Nixon RA, Mathews PM | chapter = Tissue Processing Prior to Analysis of Alzheimer's Disease Associated Proteins and Metabolites, Including Aβ | title = Amyloid Proteins | volume = 849 | pages = 493–506 | year = 2012 | pmid = 22528111 | doi = 10.1007/978-1-61779-551-0_33 | isbn = 978-1-61779-550-3 | series = Methods in Molecular Biology }}</ref><ref name="pmid22528112">{{cite book | vauthors = Schmidt SD, Mazzella MJ, Nixon RA, Mathews PM | chapter = Aβ Measurement by Enzyme-Linked Immunosorbent Assay | volume = 849 | pages = 507–27 | year = 2012 | pmid = 22528112 | doi = 10.1007/978-1-61779-551-0_34 | isbn = 978-1-61779-550-3 | series = Methods in Molecular Biology | title = Amyloid Proteins }}</ref>

[[atomic force microscope|Atomic force microscopy]], which can visualize nanoscale molecular surfaces, can be used to determine the aggregation state of amyloid beta in vitro.<ref name="pmid12499373">{{cite journal | vauthors = Stine WB, Dahlgren KN, Krafft GA, LaDu MJ | title = In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis | journal = The Journal of Biological Chemistry | volume = 278 | issue = 13 | pages = 11612–11622 | date = March 2003 | pmid = 12499373 | doi = 10.1074/jbc.M210207200 | doi-access = free }}</ref>

[[Vibrational spectroscopy|Vibrational microspectroscopy]] is a label-free method that measures the vibration of molecules in tissue samples.<ref>{{cite book | vauthors = Lasch P, Kneipp J <!-- |author-link1=Peter Lasch |author-link2=Janina Kneipp --> |date=2008 |title=Biomedical Vibrational Spectroscopy |publisher=Wiley |isbn=978-0-470-22945-3}}</ref> Amyloid proteins like Aβ can be detected with this technique because of their high content of β-sheet structures.<ref name="pmid25415602">{{cite journal | vauthors = Benseny-Cases N, Klementieva O, Cotte M, Ferrer I, Cladera J | title = Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains | journal = Analytical Chemistry | volume = 86 | issue = 24 | pages = 12047–12054 | date = December 2014 | pmid = 25415602 | doi = 10.1021/ac502667b }}</ref> 

[[Dual polarisation interferometry]] is an optical technique which can measure early stages of aggregation by measuring the molecular size and densities as the fibrils elongate.<ref name="pmid17171334">{{cite journal | vauthors = Gengler S, Gault VA, Harriott P, Hölscher C | title = Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25-35) are dependent on stimulation-protocol and genetic background | journal = Experimental Brain Research | volume = 179 | issue = 4 | pages = 621–630 | date = June 2007 | pmid = 17171334 | doi = 10.1007/s00221-006-0819-6 | s2cid = 41040399 }}</ref><ref name="pmid18005258">{{cite journal | vauthors = Rekas A, Jankova L, Thorn DC, Cappai R, Carver JA | title = Monitoring the prevention of amyloid fibril formation by alpha-crystallin. Temperature dependence and the nature of the aggregating species | journal = The FEBS Journal | volume = 274 | issue = 24 | pages = 6290–6304 | date = December 2007 | pmid = 18005258 | doi = 10.1111/j.1742-4658.2007.06144.x | s2cid = 85794556 }}</ref> These aggregate processes can also be studied on lipid bilayer constructs.<ref name="pmid19703409">{{cite journal | vauthors = Sanghera N, Swann MJ, Ronan G, Pinheiro TJ | title = Insight into early events in the aggregation of the prion protein on lipid membranes | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1788 | issue = 10 | pages = 2245–2251 | date = October 2009 | pmid = 19703409 | doi = 10.1016/j.bbamem.2009.08.005 | doi-access = free }}</ref>

== See also ==
* [[TPM21]]
* [[Sylvain Lesné]] – Aβ*56

== References ==
{{reflist}}

== External links ==
{{Wiktionary}}
* {{OMIM|104300}}

{{Amyloidosis}}

{{DEFAULTSORT:Beta Amyloid}}
[[Category:Peptides]]
[[Category:Molecular neuroscience]]
[[Category:Alzheimer's disease]]
[[Category:Amyloidosis]]
[[Category:Biomarkers]]