Back to Search
Start Over
A cortical immune network map identifies distinct microglial transcriptional programs associated with β-amyloid and Tau pathologies.
- Source :
-
Translational psychiatry [Transl Psychiatry] 2021 Jan 14; Vol. 11 (1), pp. 50. Date of Electronic Publication: 2021 Jan 14. - Publication Year :
- 2021
-
Abstract
- Microglial dysfunction has been proposed as one of the many cellular mechanisms that can contribute to the development of Alzheimer's disease (AD). Here, using a transcriptional network map of the human frontal cortex, we identify five modules of co-expressed genes related to microglia and assess their role in the neuropathologic features of AD in 540 subjects from two cohort studies of brain aging. Two of these transcriptional programs-modules 113 and 114-relate to the accumulation of β-amyloid, while module 5 relates to tau pathology. We replicate these associations in brain epigenomic data and in two independent datasets. In terms of tau, we propose that module 5, a marker of activated microglia, may lead to tau accumulation and subsequent cognitive decline. We validate our model further by showing that three representative module 5 genes (ACADVL, TRABD, and VASP) encode proteins that are upregulated in activated microglia in AD.
Details
- Language :
- English
- ISSN :
- 2158-3188
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Translational psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 33446646
- Full Text :
- https://doi.org/10.1038/s41398-020-01175-9