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Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study

Medicine and Health

Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study

B. Wu, Y. Zhang, et al.

This groundbreaking study by Bang-Sheng Wu and colleagues explores the intriguing link between brain structure and Alzheimer's disease risk. It reveals suggestive associations of cortical surface area alterations, exciting the field with potential new insights into vulnerability factors for AD.

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~3 min • Beginner • English
Abstract
Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.90, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): -43.4 (21.3), p = 0.042) and insular/isthmus cingulate (β (SE): -18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.
Publisher
Translational Psychiatry
Published On
Nov 01, 2021
Authors
Bang-Sheng Wu, Ya-Ru Zhang, Hong-Qi Li, Kevin Kuo, Shi-Dong Chen, Qiang Dong, Yong Liu, Jin-Tai Yu
Tags
Alzheimer's disease
cortical structure
Mendelian randomization
risk factors
brain surface area
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