C5aR1 antagonism suppresses inflammatory glial gene expression and alters cellular signaling in an aggressive Alzheimer's model.

ABSTRACT: Alzheimer's disease (AD) is the leading cause of dementia in older adults, and the need for effective, sustainable therapeutic targets is imperative. Pharmacologic inhibition of C5aR1 reduces plaque load, gliosis and memory deficits in animal models. However, the cellular basis underlying this neuroprotection and which processes were the consequence of amyloid reduction vs alteration of the response to amyloid were unclear. In the Arctic model, the C5aR1 antagonist PMX205 did not reduce plaque load, but deficits in short-term memory in female mice were prevented. Hippocampal single cell and single nucleus RNA-seq clusters revealed C5aR1 dependent and independent gene expression and cell-cell communication. Microglial clusters containing neurotoxic disease-associated microglial genes were r

SUBMITTER: Schartz ND 

PROVIDER: S-EPMC10473603 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature