{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:45:31Z","timestamp":1777866331630,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG074954"],"award-info":[{"award-number":["R01AG074954"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:p>For decades, amyloid \u03b2 (A\u03b2) has been the principal therapeutic target for therapies of Alzheimer's disease (AD). An alternative processing product, known as P3, may form if the amyloid precursor protein is cleaved by \u03b1\u2010secretase instead of \u03b2\u2010secretase. This shorter peptide has received little attention and is often dismissed as nonamyloidogenic and nontoxic. Our research, and that of others, has shown that the shorter peptide is anything but innocuous. We demonstrated that P3\u2014or Amyloid \u03b1 (A\u03b1) as we termed it\u2014readily forms oligomers and fibrils and is itself potentially neurotoxic and may interact with A\u03b2 to modulate the aggregation behavior and toxicity of A\u03b2. This perspective article provides a succinct overview of current uncertainties around P3\/A\u03b1. A revision of the amyloid cascade hypothesis to include P3\/A\u03b1 is urgently needed. This peptide is, most likely, not an innocent bystander, but a distinct aggregating peptide that is itself potentially neurotoxic and may be contributing to AD.<\/jats:p>","DOI":"10.1002\/cbic.202500912","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:28:27Z","timestamp":1772994507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amyloid Alpha: The Neglected Cousin of Amyloid Beta"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0082-9113","authenticated-orcid":false,"given":"Jevgenij A.","family":"Raskatov","sequence":"first","affiliation":[{"name":"Dept. of Chemistry and Biochemistry UCSC  Santa Cruz California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.07.150"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1903193"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.218"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.02.016"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222681699"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-013-9398-z"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.191262"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201900097"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191201"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00160"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c11511"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57341-4"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.148086"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201027"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116359"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121570"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemmater.5c01589"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemmater.5c02881"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121570"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202500912","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.202500912","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202500912","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:28:56Z","timestamp":1777537736000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.202500912"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,3,13]]}},"alternative-id":["10.1002\/cbic.202500912"],"URL":"https:\/\/doi.org\/10.1002\/cbic.202500912","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]},"assertion":[{"value":"2025-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500912"}}