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

被引：83

作者：

Ewers M. ^{[1
,2
]}

Biechele G. ^{[3
]}

Suárez-Calvet M. ^{[4
,5
,6
]}

Sacher C. ^{[3
]}

Blume T. ^{[2
]}

Morenas-Rodriguez E. ^{[7
]}

Deming Y. ^{[8
]}

Piccio L. ^{[9
,10
,11
]}

Cruchaga C. ^{[10
,12
]}

Kleinberger G. ^{[7
,13
]}

Shaw L. ^{[14
]}

Trojanowski J.Q. ^{[15
]}

Herms J. ^{[2
]}

Dichgans M. ^{[1
,2
,16
]}

Brendel M. ^{[3
]}

Haass C. ^{[2
,7
,16
]}

Franzmeier N. ^{[1
]}

机构：

[1] Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig Maximilian University (LMU), Munich

[2] German Center for Neurodegenerative Diseases (DZNE), Munich

[3] Department of Nuclear Medicine, University Hospital Munich, Ludwig Maximilian University Munich, Munich

[4] Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona

[5] IMIM (Hospital del Mar Medical Research Institute), Barcelona

[6] Servei de Neurologia, Hospital del Mar, Barcelona

[7] Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich

[8] Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI

[9] Department of Neurology, Washington University School of Medicine, St Louis, MO

[10] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO

[11] Brain and Mind Centre, University of Sydney, Sydney, NSW

[12] Department of Psychiatry, Washington University School of Medicine, St. Louis, MO

[13] ISAR Bioscience GmbH, Planegg

[14] Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

[15] Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

[16] Munich Cluster for Systems Neurology (SyNergy), Munich

来源：

EMBO Molecular Medicine | 2020年 / 12卷 / 9期

基金：

美国国家卫生研究院;

关键词：

beta-amyloid accumulation; microglia; protective; tau; TREM2;

D O I：

10.15252/emmm.202012308

中图分类号：

学科分类号：

摘要：

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. © 2020 The Authors. Published under the terms of the CC BY 4.0 license

引用

共 91 条

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