Preman, Pranav;
Moechars, Daan;
Fertan, Emre;
Wolfs, Leen;
Serneels, Lutgarde;
Shah, Disha;
Lamote, Jochen;
... De Strooper, Bart; + view all
(2024)
APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.
EMBO Molecular Medicine
10.1038/s44321-024-00162-7.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s44321-024-00162-7 |
| Publisher version: | http://dx.doi.org/10.1038/s44321-024-00162-7 |
| Language: | English |
| Additional information: | © 2024 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | APOE, Alzheimer’s Disease, Astrocytes, Microglia, β-amyloid Pathology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10200594 |
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