Wood, Jack I; Wong, Eugenia; Joghee, Ridwaan; Balbaa, Aya; Vitanova, Karina S; Stringer, Katie M; Vanshoiack, Alison; ... Edwards, Frances A; + view all Wood, Jack I; Wong, Eugenia; Joghee, Ridwaan; Balbaa, Aya; Vitanova, Karina S; Stringer, Katie M; Vanshoiack, Alison; Phelan, Stefan-Laural J; Launchbury, Francesca; Desai, Sneha; Tripathi, Takshashila; Hanrieder, Jörg; Cummings, Damian M; Hardy, John; Edwards, Frances A; - view fewer (2022) Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology. Cell Reports , 41 (8) , Article 111686. 10.1016/j.celrep.2022.111686.

Preview

Text wood et al 2022.pdf - Published Version Download (4MB) | Preview

Abstract

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer’s mouse model with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques. Hence, both microglial contact with plaques and functioning TREM2 are necessary for microglia to respond appropriately to amyloid pathology

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item