APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia
Year: 2024
Type: article
Abstract: The major genetic risk factor for Alzheimer's disease (AD), APOE4, accelerates beta-amyloid (Aβ) plaque formation, but whether this is caused by APOE expressed in microglia or astrocytes is debated. We express here the human APOE isoforms in astrocytes in an Apoe-deficient AD mouse model. This is not only sufficient to restore the amyloid plaque pathology but also induces the characteristic transcriptional pathological responses in Apoe-deficient microglia surrounding the plaques. We find that both APOE4 and the protective APOE2 from astrocytes increase fibrillar plaque deposition, but differentially affect soluble Aβ aggregates. Microglia and astrocytes show specific alterations in function of APOE genotype expressed in astrocytes. Our experiments indicate a central role of the astrocytes in APOE mediated amyloid plaque pathology and in the induction of associated microglia responses.
Source: EMBO Molecular Medicine
Institutions: VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, University of Cambridge, UK Dementia Research Institute, VIB-KU Leuven Center for Cancer Biology, University of Antwerp, VIB-UAntwerp Center for Molecular Neurology, Ikerbasque, Achucarro Basque Center for Neuroscience, University College London
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,890
Funders: Alzheimer's Association, UK Research and Innovation, Queen Elisabeth Medical Foundation, European Commission, Eusko Jaurlaritza, Fonds Wetenschappelijk Onderzoek, KU Leuven, Vlaams Instituut voor Biotechnologie, Ministerio de Ciencia e Innovación, Vlaamse regering, UK Dementia Research Institute, Fondation pour la Recherche sur Alzheimer, Fondation Médicale Reine Elisabeth, Medical Research Council, European Research Council, Agencia Estatal de Investigación
Awards: G121809054, Deciphering Human Astrocyte-Neuron Crosstalk in Alzheimer's disease, G1855990336, G2262748287, G2660406951, G279363373, G3480869486, G3495247720, G3681454997, G4042783231, G425668148, G434337789, G5421974903, G6272467989, G6753810669, G6860933992, G6887693182, G7084143925, The Mechanisms Of The Cellular Phase Of Alzheimer's Disease, G8936539762
OpenAlex ID: W4404242617