Title | Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Ewers M, Biechele G, Suárez-Calvet M, Sacher C, Blume T, Morenas-Rodriguez E, Deming Y, Piccio L, Cruchaga C, Kleinberger G, Shaw L, Trojanowski JQ, Herms J, Dichgans M, Brendel M, Haass C, Franzmeier N |
Corporate Authors | Alzheimer's Disease Neuroimaging Initiative(ADNI) |
Journal | EMBO Mol Med |
Volume | 12 |
Issue | 9 |
Pagination | e12308 |
Date Published | 2020 09 07 |
ISSN | 1757-4684 |
Keywords | Alzheimer Disease, Amyloid beta-Peptides, Animals, Biomarkers, Humans, Membrane Glycoproteins, Mice, Microglia, Receptors, Immunologic, tau Proteins |
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 App mouse model of amyloidosis, we studied baseline F-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. |
DOI | 10.15252/emmm.202012308 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/32790063?dopt=Abstract |
page_expo | External |
Alternate Journal | EMBO Mol Med |
PubMed ID | 32790063 |
PubMed Central ID | PMC7507349 |
Grant List | P30 AG066444 / AG / NIA NIH HHS / United States R01 AG064877 / AG / NIA NIH HHS / United States RF1 AG053303 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States RF1 AG058501 / AG / NIA NIH HHS / United States W81XWH-12-2-0012 / / U.S. Department of Defense (DOD) / International T32 AG000213 / AG / NIA NIH HHS / United States RF1 AG044546 / AG / NIA NIH HHS / United States EXC 1010 SyNergy / / Deutsche Forschungsgemeinschaft (DFG) / International P01 AG003991 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States / / LMUexcellent / International HA1737/16-1 / / Deutsche Forschungsgemeinschaft (DFG) / International |
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