Age-specific activation of microglial genes in a mouse model of AD

ABSTRACT Alzheimer’s disease (AD) is a neurodegenerative disease that increases its prevalence with age. AD is characterized by a progressive loss of cognitive function, leading to dementia. The conventional pathological hallmarks of AD include deposition of amyloid plaque, aggregation of neurofibrillary tangles, and sustained inflammation. Recent studies have confirmed that immune responses play an important role in AD progression. Single-cell RNA-sequencing (RNA-seq) studies of the AD mouse model identified the disease-associated microglia (DAM) population during AD progression, where the pro-inflammatory activity was mediated by Trem2. However, the time points and nature of DAM activation remain largely unknown. Here, we compared the time-result bulk sequencing andsingle nuclei RNA sequencing data in a mouse model of AD. We identified an age-dependent activation of Trem2 targeted immune-related genes. We showed that Trem2 affected DAM activation at an early stage (4-8 months) rather than the late stage (12-16 months). Our results highlight an age-dependent change in the Trem2-linked immune response in AD.