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Bull."],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Amyloid-\u03b2 (A\u03b2) plaques and neurofibrillary tau tangles are hallmarks of Alzheimer\u2019s disease (AD). While the intracellular localization of tau tangles within neurons nominates them as the primary producers of tau, the cellular origin of A\u03b2 is less clear as plaques accumulate extracellularly. Neurons have been considered the sole source of A\u03b2, leading to the generation of many AD animal models expressing familial AD protein variants specifically in neurons. However, emerging evidence showed that non-neuronal cells abundantly express amyloid precursor protein (APP) and its processing machinery. Among these, oligodendrocytes (OLs) exhibit the highest expression of amyloidogenic components, produce A\u03b2, and contribute to plaque burden\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here, we highlight reports on non-neuronal A\u03b2 production in the context of AD and the function of APP processing in these cells. Understanding A\u03b2 processing in non-neuronal cells might enable the identification of novel therapeutic targets, especially in humans whose brain structures differ greatly from animal models.\n                  <\/jats:p>","DOI":"10.1007\/s12264-025-01572-4","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T18:43:24Z","timestamp":1768848204000},"page":"1126-1150","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Question of Origins: Non-neuronal Sources of Amyloid-\u03b2"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-6749","authenticated-orcid":false,"given":"Andrew Octavian","family":"Sasmita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2868-6932","authenticated-orcid":false,"given":"Constanze","family":"Depp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"1572_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","volume":"7","author":"DS Knopman","year":"2021","unstructured":"Knopman DS, Amieva H, Petersen RC, Ch\u00e9telat G, Holtzman DM, Hyman BT. 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