Dataset Information

Association Between Wnt Target Genes and Cortical Volumes in Alzheimer's Disease.

ABSTRACT: The disproportionate cortical atrophy is an established biomarker for the pathophysiological process of Alzheimer's disease (AD). However, the genetic basis underlying the cortical atrophy remains poorly defined. Herein, we aim to illustrate the effect of the Wnt target genes on the cortical volumes of AD patients. 82 sporadic AD patients were recruited. All the subjects had history survey, blood biochemical examination, cognitive assessment, MRI morphometry and whole exome sequencing. This report focused on 84 common variants (minor allele frequency > 0.01) of 32 Wnt target genes, including the APC, DAAM1, DACT1, DISC1, LATS2, TLR2, WDR61, and the AXIN, DVL, FZD, LRP, TCF/LEF, WNT family genes. The Wnt target genes showed asymmetric effects on the cortical volumes of AD patients. The right temporal/parietal/occipital cortices were more affected than left temporal/parietal/occipital cortices. Nevertheless, the reverse applied to the frontal cortex. The DACT1 affected the cortical thickness most, followed by the TCF3 and APC. The DACT1 rs698025-GG genotype displayed greater right temporal pole and left medial orbito-frontal gyrus than rs698025-GA genotype (2.4 ± 0.4 vs. 2.0 ± 0.6, P = 0.005; 5.2 ± 0.6 vs. 5.0 ± 0.6, P = 0.001). The brain region most influenced by the Wnt target genes was the right calcarine cortex. In conclusion, the common variants of the Wnt target genes exert asymmetric effects on the cortical volumes of AD patients. The Wnt signaling pathway may play a role in the cortical atrophy of AD patients.

SUBMITTER: Dong L

PROVIDER: S-EPMC10754720 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Association Between Wnt Target Genes and Cortical Volumes in Alzheimer's Disease.

Dong Liling L Hou Bo B Liu Caiyan C Mao Chenhui C Huang Xinying X Shang Li L Chu Shanshan S Peng Bin B Cui Liying L Feng Feng F Gao Jing J

Journal of molecular neuroscience : MN 20231223 11-12

The disproportionate cortical atrophy is an established biomarker for the pathophysiological process of Alzheimer's disease (AD). However, the genetic basis underlying the cortical atrophy remains poorly defined. Herein, we aim to illustrate the effect of the Wnt target genes on the cortical volumes of AD patients. 82 sporadic AD patients were recruited. All the subjects had history survey, blood biochemical examination, cognitive assessment, MRI morphometry and whole exome sequencing. This repo ...[more]

PMID: 38135866

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Project description:ObjectiveWhite matter hyperintensities (WMH) are the most common neuroimaging manifestation of cerebral small vessel disease, and is frequently observed in Alzheimer's disease (AD). This study aimed to investigate the relationship between WMH and cognition and to verify the mediation of grey matter atrophy in this relationship.MethodsThe diffusion tensor imaging (DTI) technique analyses white matter fiber tract to assess white matter integrity. Voxel-based morphometry was applied to measure the grey matter volume (GMV). A linear regression model was applied to examine the associations between WMH and GMV, and mediation analyses was performed to determine the mediating role of regional GMV in the effect of WMH on cognitive function.ResultsCompared to the HC group, AD group have 8 fiber tract fractional anisotropy (FA) decreased and 16 fiber tract mean diffusivity (MD) increased. Compared to AD without WMH, AD with high WMH had 9 fiber tracts FA decreased and 13 fiber tracts MD increased. High WMH volume was negatively correlated with GMV in the frontal-parietal region. Low WMH volume was also negatively correlated with GMV except for the three regions (right angular gyrus, right superior frontal gyrus and right middle/inferior parietal gyrus), where GMV was positively correlated. Mediation analysis showed that the association between WMH and executive function or episodic memory were mediated by GMV in the frontal-parietal region.ConclusionDamage to white matter integrity was more severe in AD with WMH. Differential changes in DTI metrics may be caused by progressive myelin and axonal damage. There was a negative correlation between WMH and grey matter atrophy in frontal-parietal regions in a volume-dependent manner. This study indicates the correspondence between WMH volume and GMV in cognition, and GMV being a key modulator between WMH and cognition in AD. This result will contribute to understanding the progression of the disease process and applying targeted therapeutic intervention in the earlier stage to delay neurodegenerative changes in frontal-parietal regions to achieve better treatment outcomes and affordability.

Dataset Information

Association Between Wnt Target Genes and Cortical Volumes in Alzheimer's Disease.

Publications

Association Between Wnt Target Genes and Cortical Volumes in Alzheimer's Disease.

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