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

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 the...

Descripción completa

Detalles Bibliográficos
Autores: Ewers, Michael, Biechele, Gloria, Suárez-Calvet, Marc, Sacher, Christian, Blume, Tanja, Morenas-Rodriguez, Estrella, Deming, Yuetiva, Piccio, Laura, Cruchaga, Carlos, Kleinberger, Gernot, Shaw, Leslie, Trojanowski, John Q., Herms, Jochen, Dichgans, Martin, Alzheimer’s Disease Neuroimaging Initiative, Brendel, Matthias, Haass, Christian, Franzmeier, Nicolai
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/47940
Acceso en línea:http://hdl.handle.net/10230/47940
http://dx.doi.org/10.15252/emmm.202012308
Access Level:acceso abierto
Palabra clave:TREM2
Beta-amyloid accumulation
Microglia
Protective
Tau
Descripción
Sumario: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 18 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.

Similares en LA Referencia