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Microglial activation and tau propagate jointly across Braak stages

Authors :
Pascoal, Tharick A.
Benedet, Andrea L.
Ashton, Nicholas J.
Kang, Min Su
Therriault, Joseph
Chamoun, Mira
Savard, Melissa
Source :
Nature Medicine. September, 2021, Vol. 27 Issue 9, p1592, 8 p.
Publication Year :
2021

Abstract

Compelling experimental evidence suggests that microglial activation is involved in the spread of tau tangles over the neocortex in Alzheimer's disease (AD). We tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak-like pattern in the living human brain. We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography brain imaging for microglial activation ([.sup.11C]PBR28), amyloid-[beta] (A[beta]) ([.sup.18F]AZD4694) and tau ([.sup.18F]MK-6240) pathologies. We further assessed microglial triggering receptor expressed on myeloid cells 2 (TREM2) cerebrospinal fluid (CSF) concentrations and brain gene expression patterns. We found that [.sup.11C]PBR28 correlated with CSF soluble TREM2 and showed regional distribution resembling TREM2 gene expression. Network analysis revealed that microglial activation and tau correlated hierarchically with each other following Braak-like stages. Regression analysis revealed that the longitudinal tau propagation pathways depended on the baseline microglia network rather than the tau network circuits. The co-occurrence of A[beta], tau and microglia abnormalities was the strongest predictor of cognitive impairment in our study population. Our findings support a model where an interaction between A[beta] and activated microglia sets the pace for tau spread across Braak stages. Microglial activation and tau accumulation propagate together in patients with Alzheimer's disease, suggesting an interaction that determines disease progression.<br />Author(s): Tharick A. Pascoal [sup.1] [sup.2] [sup.3] [sup.4] , Andrea L. Benedet [sup.3] , Nicholas J. Ashton [sup.5] [sup.6] [sup.7] , Min Su Kang [sup.3] [sup.4] , Joseph Therriault [sup.3] [...]

Details

Language :
English
ISSN :
10788956
Volume :
27
Issue :
9
Database :
Gale General OneFile
Journal :
Nature Medicine
Publication Type :
Academic Journal
Accession number :
edsgcl.675425630
Full Text :
https://doi.org/10.1038/s41591-021-01456-w