Unknown

Dataset Information

0

A cortical immune network map identifies distinct microglial transcriptional programs associated with ?-amyloid and Tau pathologies.


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 ?-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.

SUBMITTER: Patrick E 

PROVIDER: S-EPMC7809035 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

A cortical immune network map identifies distinct microglial transcriptional programs associated with β-amyloid and Tau pathologies.

Patrick Ellis E   Olah Marta M   Taga Mariko M   Klein Hans-Ulrich HU   Xu Jishu J   White Charles C CC   Felsky Daniel D   Agrawal Sonal S   Gaiteri Chris C   Chibnik Lori B LB   Mostafavi Sara S   Schneider Julie A JA   Bennett David A DA   Bradshaw Elizabeth M EM   De Jager Philip L PL  

Translational psychiatry 20210114 1


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  ...[more]

Similar Datasets

| S-EPMC7901060 | biostudies-literature
| S-EPMC5391267 | biostudies-literature
| S-EPMC8357687 | biostudies-literature
| S-EPMC5651359 | biostudies-literature
| S-EPMC8758492 | biostudies-literature
| S-EPMC8203764 | biostudies-literature
| S-EPMC5760353 | biostudies-literature
| S-EPMC2909664 | biostudies-literature
| S-EPMC7016505 | biostudies-literature
| S-EPMC5719023 | biostudies-literature