한빛사논문
- 조회1,189
Seung-Hye Lee1,7, William J. Meilandt1,7,8,*, Luke Xie2, Vineela D. Gandham2, Hai Ngu3, Kai H. Barck2, Mitchell G. Rezzonico4, Jose Imperio1, Guita Lalehzadeh1, Melanie A. Huntley4, Kimberly L. Stark1. Oded Foreman3, Richard A.D. Carano2, Brad A. Friedman4, Morgan Sheng1,5, Amy Easton1, Christopher J. Bohlen1, David V. Hansen1,6,*
1Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
2Department of Biomedical Imaging, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
3Department of 3Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
4Department of Bioinformatics and Computational Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
5Present address: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
6Present address: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
7These authors contributed equally.
8Lead contact
*Corresponding author
Abstract
Loss-of-function TREM2 mutations strongly increase Alzheimer’s disease (AD) risk. Trem2 deletion has revealed protective Trem2 functions in preclinical models of β-amyloidosis, a prominent feature of pre-diagnosis AD stages. How TREM2 influences later AD stages characterized by tau-mediated neurodegeneration is unclear. To understand Trem2 function in the context of both β-amyloid and tau pathologies, we examined Trem2 deficiency in the pR5-183 mouse model expressing mutant tau alone or in TauPS2APP mice, in which β-amyloid pathology exacerbates tau pathology and neurodegeneration. Single-cell RNA sequencing in these models revealed robust disease-associated microglia (DAM) activation in TauPS2APP mice that was amyloid-dependent and Trem2-dependent. In the presence of β-amyloid pathology, Trem2 deletion further exacerbated tau accumulation and spreading and promoted brain atrophy. Without β-amyloid pathology, Trem2 deletion did not affect these processes. Therefore, TREM2 may slow AD progression and reduce tau-driven neurodegeneration by restricting the degree to which β-amyloid facilitates the spreading of pathogenic tau.
논문정보
- Research article
- 2021년 03월 (BRIC 등록일 2021-03-12)
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
