Higher CSF sTREM2 and microglia activation are associated with slower rates of beta‐amyloid accumulation

Higher CSF sTREM2 and microglia activation are associated with slower rates of beta‐amyloid accumulation

Abstract Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in th...

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Main Authors: Michael Ewers, Gloria Biechele, Marc Suárez‐Calvet, Christian Sacher, Tanja Blume, Estrella Morenas‐Rodriguez, Yuetiva Deming, Laura Piccio, Carlos Cruchaga, Gernot Kleinberger, Leslie Shaw, John Q Trojanowski, Jochen Herms, Martin Dichgans, the Alzheimer's Disease Neuroimaging Initiative (ADNI), Matthias Brendel, Christian Haass, Nicolai Franzmeier
Format: Article
Language:English
Published: Springer Nature 2020-08-01
Series:EMBO Molecular Medicine
Subjects:
beta‐amyloid accumulation
microglia
protective
tau
TREM2
Online Access:https://doi.org/10.15252/emmm.202012308
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Summary:Abstract Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid‐beta (Aβ) accumulation remains unclear. To address this question, we pursued a two‐pronged translational approach. Firstly, in non‐demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross‐sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated with attenuated amyloid PET increase and lower tau PET. Secondly, in the AppNL‐G-F mouse model of amyloidosis, we studied baseline 18F‐GE180 microglia PET and longitudinal amyloid PET to test the microglia vs. Aβ association, without any confounding co‐pathologies often present in AD patients. Higher microglia PET at age 5 months was associated with a slower amyloid PET increase between ages 5‐to‐10 months. In conclusion, higher microglia activation as determined by CSF sTREM2 or microglia PET shows protective effects on subsequent amyloid accumulation.
ISSN:1757-4676
1757-4684

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