GPNMB+ microglia moderate the amyloid beta-tau interaction in early Alzheimer’s disease

Abstract

SummaryAlthough interactions between amyloid-beta (Aβ) and tau proteins have been implicated in Alzheimer’s disease (AD), the detailed mechanisms by which these interactions contribute to disease progression remain unclear. In this study, we evaluated proteomics and protein–protein interaction data using BIONC, a deep learning-based network integration method to investigate factors moderating the effects of the Aβ-tau interaction in mild cognitive impairment and early-stage AD. Our results suggested that astrocytes and GPNMB+ microglia moderate the Aβ-tau interaction. Based on linear regression with histopathological and gene expression data, GFAP and IBA1 levels andGPNMBgene expression positively contributed to the interaction of tau with Aβ in non-dementia cases, replicating the results of the network analysis. These findings indicate that GPNMB+ microglia moderate the Aβ-tau interaction in early AD and therefore are a novel therapeutic target.Graphical Abstract