The Influence of MTHFR Polymorphism on Gray Matter Volume in Patients With Amnestic Mild Cognitive Impairment

Area of Science:

• Neuroscience
• Genetics
• Radiology

Background:

• Alzheimer's disease (AD) pathogenesis is linked to the methylenetetrahydrofolate reductase (MTHFR) gene.
• Amnestic mild cognitive impairment (aMCI) is a precursor to dementia with high Alzheimer's disease progression risk.
• Apolipoprotein E (APOE) gene's effects on aMCI structural changes are known, but MTHFR C677T and MTHFR × APOE interactions on gray matter atrophy are understudied.

Purpose of the Study:

• To investigate the effects of MTHFR C677T genotype and MTHFR × APOE genotype interactions on gray matter atrophy in aMCI patients.
• To compare gray matter volume differences between aMCI patients and healthy controls.
• To identify specific brain regions affected by these genetic factors in aMCI.

Main Methods:

• Voxel-based morphometry (VBM) analysis was employed.
• Sixty aMCI patients and 30 healthy controls were recruited for the study.
• Genotyping for MTHFR C677T and Apolipoprotein E (APOE) was performed.

Main Results:

• aMCI patients exhibited significant gray matter atrophy in the bilateral hippocampus, right parahippocampal gyrus, and left superior temporal gyrus compared to controls.
• APOE ε4 carriers within the aMCI group showed reduced gray matter volume in the right hippocampus versus non-carriers.
• A significant interaction between diagnosis and MTHFR C677T genotype on the right precuneus was observed in individuals without the APOE ε4 allele.

Conclusions:

• Findings suggest MTHFR C677T genotype influences brain structural alterations in aMCI.
• The study provides evidence for the interplay between MTHFR and APOE genotypes in aMCI-related brain changes.
• These genetic factors may contribute to the progression from aMCI to Alzheimer's disease.