이승재 (서울대학교 의과대학)

한빛사논문

조회238

서울대학교 의과대학

CV File 398 kb

Brain, Aug 28 2024, awae221 | https://doi.org/10.1093/brain/awae221 Amyloid-β-activated microglia can induce compound proteinopathies

Sang Hwan Lee,^1,2 Eun-Jin Bae,^1,2 Dayana Perez-Acuna,¹ Min Kyo Jung,³ Jong Won Han,^1,4 Inhee Mook-Jung^1,2,4,5 and Seung-Jae Lee^1,2,5

¹Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea

²Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea

³Neural Circuits Research Group, Korea Brain Research Institute, Daegu 41068, Korea

⁴Department of Biochemistry, Seoul National University College of Medicine, Seoul 03080, Korea

⁵Convergence Research Center for Dementia, Medical Research Center, Seoul National University, Seoul 03080, Korea

Correspondence to: Seung-Jae Lee

Abstract

Neuropathological features of Alzheimer's disease include amyloid plaques, neurofibrillary tangles and Lewy bodies, with the former preceding the latter two. However, it is not fully understood how these compound proteinopathies are interconnected. Here, we show that transplantation of amyloid-β oligomer-activated microglia into the striatum of naïve mice was sufficient to generate all the features of Alzheimer's disease, including widespread tauopathy and synucleinopathy, gliosis, neuroinflammation, synapse loss, neuronal death, and cognitive and motor deficits. These pathological features were eliminated by microglia depletion and anti-inflammatory drug administration. Our results suggest the crucial roles of microglia-driven inflammation in development of mixed pathology. This study provides not only mechanistic insights into amyloid-β oligomer-triggered proteinopathies but also a novel animal model recapitulating the salient features of Alzheimer's disease.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-29)
연구진국내 연구진
분야 의약학 > 신경의학

댓글 작성 로그인

CV 열람하기

연락처 보기