Abstract
INTRODUCTION
The triggering receptor expressed on myeloid cells 2 (TREM2) arginine-47-histidine (R47H) mutation is a significant risk for Alzheimer’s disease (AD) with unclear mechanisms. Previous studies focused on microglial amyloid-β (Aβ) phagocytosis with less attention on the impact of TREM2R47H mutation on blood monocytes.
METHODS
Bone marrow transplantation (BMT) models were used to assess the contribution of blood monocytes carrying TREM2R47H mutation to AD.
RESULTS
Aβ phagocytosis was compromised in mouse monocytes carrying the TREM2R47H mutation. Transplantation of bone marrow cells (BMCs) carrying TREM2R47H mutation increased cerebral Aβ burden and aggravated AD-type pathologies. Moreover, the replacement of TREM2R47H-BMCs restored monocytic Aβ phagocytosis, lowered Aβ levels in the blood and brain, and improved cognitive function.
DISCUSSION
Our study reveals that blood monocytes carrying the TREM2R47H mutation substantially contribute to the pathogenesis of AD, and correcting the TREM2R47H mutation in BMCs would be a potential therapeutic approach for those carrying this mutation.
Highlights
TREM2R47H mutation compromises the Aβ phagocytosis of blood monocytes.
Blood monocytes carrying TREM2R47H mutation contribute substantially to AD pathogenesis.
Correction of the TREM2R47H mutation in bone marrow cells ameliorates AD pathologies and cognitive impairments.
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This post is Copyright: Zhong‐Yuan Yu,
Jie Liu,
Zhi‐Hao Liu,
Xiao‐Yu Liu,
Jin‐Mei Tuo,
Jiang‐Hui Li,
Yun‐Feng Tu,
Qi Tan,
Yuan‐Yuan Ma,
Yu‐Di Bai,
Jia‐Yan Xin,
Shan Huang,
Gui‐Hua Zeng,
An‐Yu Shi,
Jun Wang,
Yu‐Hui Liu,
Xian‐Le Bu,
Li‐Lin Ye,
Ying Wan,
Tong‐Fei Liu,
Xiao‐Wei Chen,
Zi‐Long Qiu,
Chang‐Yue Gao,
Yan‐Jiang Wang | December 31, 2024