{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sun Z"],"funding":["NIA NIH HHS","NIMH NIH HHS","NINDS NIH HHS"],"pagination":["adl2992"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11787906"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["385(6708)"],"pubmed_abstract":["Late-onset Alzheimer's disease (LOAD) is the most common form of Alzheimer's disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)-based direct reprogramming of fibroblasts from individuals affected by autosomal dominant AD (ADAD) and LOAD in a three-dimensional environment effectively recapitulate key neuropathological features of AD. Reprogrammed LOAD neurons exhibit Aβ-dependent neurodegeneration, and treatment with β- or γ-secretase inhibitors before (but not subsequent to) Aβ deposit formation mitigated neuronal death. Moreover inhibiting age-associated retrotransposable elements in LOAD neur"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Modeling late-onset Alzheimer's disease neuropathology via direct neuronal reprogramming."],"pmcid":["PMC11787906"],"funding_grant_id":["P30 AG066444","R01 MH123748","RF1 AG056296","R01 AG078964","R01 NS107488"],"pubmed_authors":["Houlden H","Sato C","Lu X","Valdez C","Mennerick SJ","Ren Y","Holtzman DM","Karahan H","Bateman RJ","Kim J","Kwon JS","Sun Z","Cates K","Fitzpatrick JAJ","Karch CM","Yoo AS","Tanzi RE","Sviben S","Diamond MI","Chen S","Walker CK"],"additional_accession":[]},"is_claimable":false,"name":"Modeling late-onset Alzheimer's disease neuropathology via direct neuronal reprogramming.","description":"Late-onset Alzheimer's disease (LOAD) is the most common form of Alzheimer's disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)-based direct reprogramming of fibroblasts from individuals affected by autosomal dominant AD (ADAD) and LOAD in a three-dimensional environment effectively recapitulate key neuropathological features of AD. Reprogrammed LOAD neurons exhibit Aβ-dependent neurodegeneration, and treatment with β- or γ-secretase inhibitors before (but not subsequent to) Aβ deposit formation mitigated neuronal death. Moreover inhibiting age-associated retrotransposable elements in LOAD neur","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2025-04-03T23:36:51.832Z","creation":"2025-04-03T23:36:51.832Z"},"accession":"S-EPMC11787906","cross_references":{"pubmed":["39088624"],"doi":["10.1126/science.adl2992"]}}