CXCR4 as a Modifier of Tau Aggregation in Alzheimer's Disease

Principal Investigator

Project Goals

Several lines of evidence suggest that inflammation and altered function of the cell types in the brain involved in inflammation, such as microglia, represent an early and critical driver of Alzheimer’s disease (AD). Our group has recently shown that a chemokine receptor type 4 (CXCR4) found in the cell types that mediate inflammation in the brain, such as microglia, contributes to tauopathies, such as progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration, and AD. The objective of this study is to begin to determine how CXCR4 drives AD. Together, the findings from this study will define the function of a new gene that increases risk for AD and other tauopathies and will shed light on its role in disease processes.

Project Summary

Changes in the cell types in the brain involved in inflammation, such as microglia, represent an early and critical driver of Alzheimer’s disease (AD). Our group has recently shown that a gene found in the cell types that control inflammation in the brain, such as microglia, contributes to tauopathies such as progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration, and AD. The objective of this study is to begin to determine how this gene drives AD. To do this, we will use functional genomics and cell biological approaches in human tissue and stem cell models, and we will target this gene in a mouse model of tauopathy to define the effects of this gene on disease course in vivo. Together, the findings from this study will define the function of a new gene that increases risk for AD and other tauopathies and will shed light on its role in disease processes.

Publications

Karch CM, Kao AW, Karydas A, Onanuga K, Martinez R, Argouarch A, Wang C, Huang C, Sohn PD, Bowles KR, Spina S, Silva MC, Marsh JA, Hsu S, Pugh DA, Ghoshal N, Norton J, Huang Y, Lee SE, Seeley WW, Theofilas P, Grinberg LT, Moreno F, McIlroy K, Boeve BF, Cairns NJ, Crary JF, Haggarty SJ, Ichida JK, Kosik KS, Miller BL, Gan L, Goate AM, Temple S; Tau Consortium Stem Cell Group. A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies. Stem Cell Reports. 2019 Oct 4. pii: S2213-6711(19)30335-2. doi: 10.1016/j.stemcr.2019.09.006. [Epub ahead of print] PubMed PMID: 31631020 PubMed Icon Google Scholar Icon

First published on: September 27, 2018

Last modified on: November 25, 2024