Trem2 H157Y increases soluble TREM2 production and reduces amyloid pathology.
Wenhui QiaoYixing ChenJun ZhongBenjamin J MaddenCristine M CharlesworthYuka A MartensChia-Chen LiuJoshua KnightTadafumi C IkezuKurti AisheYiyang ZhuAxel MenesesCassandra L RosenbergLindsey A KuchenbeckerLucy K VanmaeleFuyao LiKai ChenFrancis ShueMaxwell V DacquelJohn FryerAkhilesh PandeyNa ZhaoGuojun BuPublished in: Molecular neurodegeneration (2023)
Taken together, our findings suggest beneficial effects of the Trem2 H157Y mutation in synaptic function and in mitigating amyloid pathology. Considering the genetic association of TREM2 p.H157Y with AD risk, we speculate TREM2 H157Y in humans might increase AD risk through an amyloid-independent pathway, such as its effects on tauopathy and neurodegeneration which merit further investigation.
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