Neuroticism alters the transcriptome of the frontal cortex to contribute to the cognitive decline and onset of Alzheimer's disease

Abstract

Accumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimers disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, {beta}-amyloid (A{beta}) and phosphorylated tangles (TAU). However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brains transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibus P=0.005) but not the other 4 personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P<0.05) with four neuronal modules, which are more related to PHFtau than A{beta} across all eight brain regions. Furthermore, the effect of neuroticism on cognitive decline and AD might be mediated through the expression of module 7 and TAU pathology (P=0.008). To conclude, neuroticism has overall impact on human brains transcriptome and its effect on cognitive decline and AD might be mediated through TAU pathology related gene transcription mechanism.