Alzheimer's disease and diabetes-associated cognitive dysfunction: the microglia link?

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and the aggregation of tau protein, resulting in intense memory loss and dementia. Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus, which is associated with decreased cognitive function and impaired memory. A growing body of literature emphasize the involvement of microglia in AD and DACD. Although AD and DACD share some common features related to symptomatology and pathophysiology, the characteristics and heterogeneity of microglia remain largely unknown in these two diseases. In this study, multiple bioinformatics analyses were performed to analyze the frequency, altered genes, cell-cell communication, and subtypes of microglia in AD and DACD mouse models based on two publicly single-nucleus RNA sequencing (snRNA-Seq) datasets. The results revealed that the frequency of microglia was increased in both AD and DACD mouse models when compared with control mice. After analyzing the differentially expressed genes of microglia from the two mouse models, only six common upregulated genes were found. The CellChat analysis revealed the complex cell-cell communication network (microglia clusters with other cell types) in 5XFAD vs. control mice and db/db vs. control mice. The microglia subtypes and their transcription factor activity profile in 5XFAD mice were different from that in db/db mice. In summary, this study provided some insights into the alterations of microglia in 5XFAD and db/db mice, which might open up potential avenues for the microglial-targeted therapy in AD and DACD.