TY - JOUR
T1 - Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation
AU - Ewers, Michael
AU - Biechele, Gloria
AU - Suárez-Calvet, Marc
AU - Sacher, Christian
AU - Blume, Tanja
AU - Morenas-Rodriguez, Estrella
AU - Deming, Yuetiva
AU - Piccio, Laura
AU - Cruchaga, Carlos
AU - Kleinberger, Gernot
AU - Shaw, Leslie
AU - Trojanowski, John Q.
AU - Herms, Jochen
AU - Dichgans, Martin
AU - Brendel, Matthias
AU - Haass, Christian
AU - Franzmeier, Nicolai
N1 - Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2020/9/7
Y1 - 2020/9/7
N2 - 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.
AB - 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.
KW - TREM2
KW - beta-amyloid accumulation
KW - microglia
KW - protective
KW - tau
UR - http://www.scopus.com/inward/record.url?scp=85089135794&partnerID=8YFLogxK
U2 - 10.15252/emmm.202012308
DO - 10.15252/emmm.202012308
M3 - Article
C2 - 32790063
AN - SCOPUS:85089135794
SN - 1757-4676
VL - 12
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 9
M1 - e12308
ER -