{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rajani RM"],"funding":["Alzheimer’s Association","National Centre for the Replacement, Refinement and Reduction of Animals in Research","UK Dementia Research Institute","Medical Research Council","Alzheimer's Association","National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre"],"pagination":["e3002727"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11265669"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(7)"],"pubmed_abstract":["Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Aβ in the human brain and play a key role in promoting abnormal neuronal hyperactivity in an AD knock-in mouse model. We show that selectively suppressing oligodendrocyte Aβ production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD."],"journal":["PLoS biology"],"pubmed_title":["Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease."],"pmcid":["PMC11265669"],"funding_grant_id":["MR/X011038/1","AARF-23 1149637","23AARFD-1029918","MR/X019977/1","NC/W001675/1","UKDRI-1018"],"pubmed_authors":["Harris SS","Taso OS","Lam FKW","Danial JSH","Busche MA","Ellingford R","Hellmuth M","Sala Frigerio C","Rajani RM","Klenerman D","Vassar R","Wray S","Bourdenx M","Arber C","Fertan E","Graykowski D","Swire M","Giovannucci TA","Lloyd M"],"additional_accession":[]},"is_claimable":false,"name":"Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease.","description":"Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Aβ in the human brain and play a key role in promoting abnormal neuronal hyperactivity in an AD knock-in mouse model. We show that selectively suppressing oligodendrocyte Aβ production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-02T23:12:32.552Z","creation":"2025-04-06T12:30:58.59Z"},"accession":"S-EPMC11265669","cross_references":{"pubmed":["39042667"],"doi":["10.1371/journal.pbio.3002727"]}}