陶氏病
小胶质细胞
生物
淀粉样蛋白(真菌学)
突变
PSEN1型
细胞生物学
神经退行性变
阿尔茨海默病
分子生物学
炎症
免疫学
早老素
病理
疾病
遗传学
基因
医学
植物
作者
Yun Chen,Sihui Song,Samira Parhizkar,J.Michard Lord,Yiyang Zhu,Michael R. Strickland,Chanung Wang,Jiyu Park,G. Travis Tabor,Hong Jiang,Kevin Li,Albert A. Davis,Carla M. Yuede,Marco Colonna,Jason D. Ulrich,David M. Holtzman
出处
期刊:Cell
[Elsevier]
日期:2024-01-01
卷期号:187 (2): 428-445.e20
被引量:20
标识
DOI:10.1016/j.cell.2023.11.029
摘要
A recent case report described an individual who was a homozygous carrier of the APOE3 Christchurch (APOE3ch) mutation and resistant to autosomal dominant Alzheimer’s Disease (AD) caused by a PSEN1-E280A mutation. Whether APOE3ch contributed to the protective effect remains unclear. We generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-β (Aβ) plaque-depositing model. We injected AD-tau brain extract to investigate tau seeding and spreading in the presence or absence of amyloid. Similar to the case report, APOE3ch expression resulted in peripheral dyslipidemia and a marked reduction in plaque-associated tau pathology. Additionally, we observed decreased amyloid response and enhanced microglial response around plaques. We also demonstrate increased myeloid cell phagocytosis and degradation of tau aggregates linked to weaker APOE3ch binding to heparin sulfate proteoglycans. APOE3ch influences the microglial response to Aβ plaques, which suppresses Aβ-induced tau seeding and spreading. The results reveal new possibilities to target Aβ-induced tauopathy.
科研通智能强力驱动
Strongly Powered by AbleSci AI