Comparative profiling of cortical gene expression in Alzheimer’s disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation

Alzheimer’s disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and theAppNL-G-F/NL-G-Fand 3xTg-AD-H mouse models. Genes commonly altered inAppNL-G-F/NL-G-Fand human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b,Cd74,Ctss,Gfap,Nfe2l2,Phyhd1,S100b,Tf,Tgfbr2, andVim) was increased in theAppNL-G-F/NL-G-Fcortex as Aβ amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. TheAppNL-G-F/NL-G-Fcortex also had altered expression of genes (Abi3,Apoe,Bin2,Cd33,Ctsc,Dock2,Fcer1g,Frmd6,Hck,Inpp5D,Ly86,Plcg2,Trem2,Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.