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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 Alzheimer's disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, ?-amyloid (A?) 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 brain's 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 four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P?

SUBMITTER: De Jager CH

PROVIDER: S-EPMC7904919 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

De Jager Céline H CH White Charles C CC Bennett David A DA Ma Yiyi Y

Translational psychiatry 20210224 1

Accumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimer's disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, β-amyloid (Aβ) 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 brain's transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism h ...[more]

PMID: 33627625

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Project description:Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD.

Dataset Information

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

Publications

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

Similar Datasets

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