{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:04:02Z","timestamp":1791187442116,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,11,8]]},"abstract":"<jats:p>The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE is found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks of the disease. Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated protein tau. In vitro, tau binds avidly to apoE3, but not to apoE4, forming a bimolecular complex. Tau phosphorylated with a brain extract does not bind either isoform. ApoE3 binds to the microtubule-binding repeat region of tau, which is also the region that is thought to cause self-assembly into the paired helical filament. Binding studies with fragments of ApoE demonstrate that the tau-binding region of apoE3 corresponds to its receptor-binding domain and is distinct from the region that binds lipoprotein particles or beta\/A4 peptide. Isoform-specific interactions of apoE with tau may regulate intraneuronal tau metabolism in Alzheimer disease and alter the rate of formation of paired helical filaments and neurofibrillary tangles.<\/jats:p>","DOI":"10.1073\/pnas.91.23.11183","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:59:11Z","timestamp":1149065951000},"page":"11183-11186","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":372,"title":["Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease."],"prefix":"10.1073","volume":"91","author":[{"given":"W J","family":"Strittmatter","sequence":"first","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Goedert","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K H","family":"Weisgraber","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Jakes","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Y","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pericak-Vance","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Schmechel","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A D","family":"Roses","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,11,8]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.23.11183","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:58:35Z","timestamp":1649858315000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.23.11183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,11,8]]},"references-count":0,"journal-issue":{"issue":"23","published-print":{"date-parts":[[1994,11,8]]}},"alternative-id":["10.1073\/pnas.91.23.11183"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.23.11183","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,11,8]]},"assertion":[{"value":"1994-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}