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

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Alzheimer's disease (AD) is characterized by progressive neuronal loss, often involving brain atrophy.
• The causal link between specific cortical structural changes and AD risk remains unclear.
• Understanding these relationships is crucial for developing targeted interventions for AD.

Purpose of the Study:

• To investigate the potential causal relationship between cortical structure (surface area and thickness) and Alzheimer's disease risk using a bidirectional Mendelian randomization approach.
• To examine the association of whole cortex and 34 regional cortical structures with AD.
• To explore the potential causal effect of AD vulnerability on cortical structure.

Main Methods:

• Bidirectional two-sample Mendelian randomization analysis.
• Utilized genetic variants from large genome-wide association studies for cortical structure and AD.
• Analyzed surface area and thickness of the whole cortex and 34 cortical regions.

Main Results:

• Suggestive evidence indicated that decreased surface area of the temporal pole and decreased thickness of the cuneus are associated with higher AD risk.
• A suggestive association was found between AD vulnerability and decreased surface area of the precentral and isthmus cingulate regions.
• No statistically significant causal relationships met Bonferroni correction thresholds.

Conclusions:

• Suggestive evidence supports an association between atrophy in the temporal pole and cuneus and increased risk of Alzheimer's disease.
• Suggestive evidence indicates a potential causal relationship between AD vulnerability and reduced surface area in the precentral and isthmus cingulate cortices.
• Findings contribute to understanding the complex interplay between cortical structure and AD pathogenesis.