{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:50:12Z","timestamp":1791186612927,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[1995,3,1]],"date-time":"1995-03-01T00:00:00Z","timestamp":794016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[1995,3]]},"abstract":"<jats:p>\n                    A major histopathological hallmark of Alzheimer's disease (AD) is the presence of amyloid deposits in the parenchyma of the amygdala, hippocampus, and neocortex. The principal component of amyloid is the \u03b2\u2010amyloid protein (A\u03b2), a 3943 amino acid peptide composed of a portion of the transmembrane domain and the extracellular domain of the amyloid precursor protein (APP). APP occurs as several A\u03b2\u2010containing isoforms of 695, 751, and 770 amino acids, with the latter two APP containing a domain that shares structural and functional homologies with Kunitz serine protease inhibitors. In cultured cells, APP mature through the constitutive secretory pathway, and some cell surface\u2010bound APP are cleaved by an enzyme, designated as \u03b1\u2010secretase, within the A\u03b2 domain, an event that precludes A\u03b2 amyloidogenesis. Several studies have delineated two additional pathways of APP processing: first, an endosomal\/lysosomal pathway generates a complex set of APP\u2010related membrane\u2010bound fragments, some of which contain the entire A\u03b2 sequence; and, second, by mechanisms which are not fully understood, A\u03b21\u201340 is secreted into the conditioned medium in vitro and is present in cerebrospinal fluid in vivo. The intracellular sites of enzymes responsible for proteolytic cleavage at the NH2 and COOH termini of A\u03b2, termed \u03b3\u2010 and \u03b2\u2010secretase, respectively, have not been identified. Finally, recent molecular genetic investigations have identified a variety of mutations in APP that segregate with early\u2010onset familial AD and with hereditary cerebral hemorrhage with amyloid, Dutch type (HCHWA\u2010D). Several of these mutations appear to influence APP processing and result in the production of higher levels or longer A\u03b2\u2010related peptides that are inherently more fibrillogenic. Although a variety of lines of evidence implicates APP\/A\u03b2 in AD, the mechanisms by which A\u03b2 influences the biology and vulnerability of neural cells are not fully understood but are very active areas of investigation. This review focuses on the present state of our understanding of APP and A\u03b2 in the context of AD.\u2014Sisodia, S. S., Price, D. L. Role of the \u03b2\u2010amyloid protein in Alzheimer's disease\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    9, 366\u2013370 (1995)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.9.5.7896005","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T05:13:14Z","timestamp":1516252394000},"page":"366-370","source":"Crossref","is-referenced-by-count":218,"title":["Role of the \u03b2\u2010amyloid protein in Alzheimer's disease"],"prefix":"10.1096","volume":"9","author":[{"given":"Sangram S.","family":"Sisodia","sequence":"first","affiliation":[{"name":"Department of Pathology Department of Neurology, and Department of Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Laboratory The Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1995,3]]},"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fasebj.9.5.7896005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fasebj.9.5.7896005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:27:33Z","timestamp":1761665253000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fasebj.9.5.7896005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,3]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1995,3]]}},"alternative-id":["10.1096\/fasebj.9.5.7896005"],"URL":"https:\/\/doi.org\/10.1096\/fasebj.9.5.7896005","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,3]]}}}