CIMR-Neuroimmune Mechanisms of Alzheimer’s Disease

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Neuroimmune Mechanisms of Alzheimer’s Disease

Date：2024-10-09

NO. 42

CIMR Wednesday Lecture Series

Time:

Wednesday, Oct. 9 2024, 4:00 p.m.

Location:

Yifu Lecture Hall, North Basic Research Building

Host：

Guoliang Chai (柴国梁)

Investigator

Chinese Institutes for Medical Research

Speaker：

Xin Wang (王鑫)

Professor

Institute of Neuroscience

Xiamen University

TITLE：

Neuroimmune Mechanisms of Alzheimer's Disease

ABSTRACT:

β2-microglobulin (B2M), a critical component of MHC-I and an amyloid itself, emerges as a key player in Alzheimer's disease (AD). Our research reveals B2M co-aggregates with β-amyloid (Aβ), exacerbating pathology. Inhibiting B2M-Aβ co-aggregation significantly reduces amyloid pathology and cognitive deficits in AD models. Crucially, peripheral B2M crosses the blood-brain barrier, impacting brain pathology, while its clearance provides neuroprotection. Given current AD treatments' limitations, our findings position B2M as a promising novel therapeutic target, potentially transforming AD intervention strategies.

SELECTED PAPERS

1. Gao Y, Hong Y, Huang L, Zheng S, Zhang H, Wang S, Yao Y, Zhao Y, Zhu L, Xu Q, Chai X, Zeng Y, Zeng Y, Zheng L, Zhou Y, Luo H, Zhang X, Zhang H, Zhou Y, Fu G, Sun H, Huang TY, Zheng Q, Xu H, Wang X. β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function. Cell. 2023;186(5):1026-1038.

2. Zhao Y, Zheng Q, Hong Y, Gao Y, Hu J, Lang M, Zhang H, Zhou Y, Luo H, Zhang X, Sun H, Yan XX, Huang TY, Wang YJ, Xu H, Liu C, Wang X. β2-microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023. 2023;26(7):1170-1184.

3. Zheng Q, Song B, Li G, Cai F, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang X-F, Luo H, Zhang X, Zhang H, Zeng Z, Huang T, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H, Song W, and Wang X. USP25 inhibition ameliorates Alzheimer’s pathology through regulating APP processing and Aβ generation. J Clin Invest. 2022;132(5): e15217.