A cortical immune network map identifies a subset of human microglia involved in Tau pathology
Charles C White,
Lori B Chibnik,
Julie A Schneider,
David A. Bennett,
Elizabeth M Bradshaw,
Philip L. De Jager
Posted 14 Dec 2017
bioRxiv DOI: 10.1101/234351
Posted 14 Dec 2017
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 gene modules of coexpressed genes related to microglia and assess their role in the neuropathologic features of AD in 541 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. These modules are also detectable in the human brain's epigenome, where we replicate these associations. 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 VASP, a representative module 5 gene, encodes a protein that is upregulated in activated microglia in AD.
- Downloaded 954 times
- Download rankings, all-time:
- Site-wide: 13,201 out of 94,912
- In neuroscience: 2,089 out of 16,862
- Year to date:
- Site-wide: 44,898 out of 94,912
- Since beginning of last month:
- Site-wide: 38,184 out of 94,912
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!