{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:54:05Z","timestamp":1782273245701,"version":"3.54.5"},"reference-count":52,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Electron cryo-microscopy (cryo-EM) has made it possible to determine near-atomic structures of \u03c4 filaments from human brain. Previous work had shown that the cores of paired helical and straight filaments of Alzheimer's disease are made of two identical, but differently arranged C-shaped protofilaments. In recent years, cryo-EM has shown that the Alzheimer \u03c4 fold is 79 amino acids long. Five of the eight \u03b2-strands give rise to two antiparallel \u03b2-sheets, with the other three forming a \u03b2-helix. High-affinity binding sites of positron emission tomography ligand APN-1607 (PM-PBB3) are in the \u03b2-helix region. The Alzheimer fold contrasts with the 94 amino acid-long Pick fold, which is J-shaped and comprises nine \u03b2-strands that give rise to four antiparallel \u03b2-sheets, in the absence of a \u03b2-helix. Chronic traumatic encephalopathy \u03c4 fold is similar to the Alzheimer fold, but differs in the \u03b2-helix region, which is larger and contains a non-proteinaceous density that is probably hydrophobic. These folds are mostly two-layered. By contrast, the 107 amino acid \u03c4 fold of the 4R tauopathy corticobasal degeneration is four-layered and comprises 11 \u03b2-strands. It contains an internal, probably hydrophilic, density that is surrounded by \u03c4. The \u03c4 folds described here\u00a0share the presence of microtubule-binding repeats 3 and 4, as well as 10\u201313 amino acids after repeat 4.<\/jats:p>","DOI":"10.1042\/ebc20210025","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T13:36:04Z","timestamp":1638279364000},"page":"949-959","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cryo-EM structures of \u03c4 filaments from human brain"],"prefix":"10.1042","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7886","authenticated-orcid":false,"given":"Michel","family":"Goedert","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"2021122211014572400_B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1146\/annurev-neuro-072116-031153","article-title":"Propagation of tau aggregates and neurodegeneration","volume":"40","author":"Goedert","year":"2017","journal-title":"Annu. 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