AUTHOR=Cai Suping , Huang Kexin , Yang Fan , Wang Xuwen , Wu Sijia , Wang Yubo , Huang Liyu 

TITLE=Cortical Thickness Differences Are Associated With Chemical Synaptic Transmission Upregulated Genes in Degeneration of Mild Cognitive Impairment

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 13 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.745381

DOI=10.3389/fnagi.2021.745381

ISSN=1663-4365

ABSTRACT=Mild cognitive impairment (MCI) is a transition between normal cognition (NC) and Alzheimer's disease (AD). Differences in cortical thickness (ΔCT) have been reported in individuals who degenerate from MCI to AD. The aspects of genetic and transcriptional variation related to ΔCT is vague. In this study, using an eight-year longitudinal tracking label, we investigated the genetic correlates of ΔCT in MCI subjects who degenerated from MCI to AD (MCI_AD). We employed partial least squares regression (PLSR) on brain T1-MRI images of 180 participants (143 stable MCI participants and 37 MCI_AD participants) and brain gene expression data from the Allen Institute for Brain Science (AIBS) database to investigate the genes associated with ΔCT. We revealed that upregulated genes in PLSR component 1 genes were enriched in chemical synaptic transmission and interpreted remarkable variation in ΔCT. To verify the robustness and specificity of the results, we conducted PLSR analysis in the validation dataset and specificity dataset and performed weighted gene co-expression network analysis instead of PLSR in the above three datasets. We also used gene expression data in the brain prefrontal cortex from the Gene Expression Omnibus (GEO) database to indirectly validate the robustness and specificity of our results. We conclude that transcriptionally upregulated genes with chemical synaptic transmission are robustly related to global ΔCT in MCI patients who degenerated from MCI to AD.