Increased Maternal Compared to Paternal Transmission of Alzheimer's Disease May Be Due to Increased Incidence of Depression in Women.

ABSTRACT

BACKGROUND: Mothers transmit Alzheimer's disease (AD) more frequently than fathers. Factors other than female longevity may be at work to promote maternal transmission of AD. Among these are the X chromosome, mitochondrial DNA, and AD comorbidities, especially depression. A recent study associated mitochondrial SNP rs2853499 with AD. MATERIALS AND METHODS: We used UK Biobank (UKBB) data to investigate the relation of mitochondrial SNP rs2853499, with AD. To identify cases of AD we used ICD10 code G30.9. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai. We used PLINK, a whole-genome association analysis toolset, to analyze the UKB22418 mitochondrial hard-called chromosome file. RESULTS: Of 953 AD cases, 493 were male (51.7%) and 460 were female (48.3%). Mothers were twice as likely to transmit AD compared to fathers. We found that in individuals with AD, 22.3% (n=201) carried the A allele of SNP rs2853499, 77.7% (n=700) carried the G allele. In individuals without AD, 22.2% (n=10,7726) carried the A allele of SNP rs2853499, 77.8% (n=378,535) carried the G allele. This difference was not significant (p=0.91, two-tailed Fisher exact test). Therefore, factors other than mitochondrial SNP rs2853499 may be at work to promote maternal transmission of AD. CONCLUSION: We conclude that depression, a multigenic illness, in the mother is most likely the basis for the fact that mothers transmit AD twice as often as fathers.