The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease and case-control studies suggest that the APOE4 link is stronger in women. Altmann and colleagues examined the APOE4-by-sex interaction in conversion risk and cerebrospinal fluid biomarker levels. In controls, both male and female APOE4-carriers were more likely to convert to Mild Cognitive Impairment(MCI)/Alzheimers(AD), but the effect was stronger in women. For patients with MCI, both male and female APOE4 carriers were more likely to convert to Alzheimers. Biomarker results suggested that increased APOE-related risk in women may be associated with tau pathology. Others point to hormones to explain the APOE4 gender bias. The APOE DNA contains estrogen binding sites and mouse studies show that estrogen can regulate APOE expression in a tissue-specific manner. Human data show that cells age faster in female APOE4 carriers but less so in women on hormone therapy. These data point to new directions in Alzheimer research and treatment.
Altmann A, Tian L, Henderson VW, Grecius MD; for the ADNI Investigators: Sex modifies the APOE-related risk of developing Alzheimer’s disease. Ann. Neurol. [Epub ahead of print, March 13, 2014; doi: 10.1002/ana.24135 ].
