Increased risk of dementia in mothers of Alzheimer's disease cases: evidence for maternal inheritance

Abstract

This study tests the hypothesis of maternal inheritance of AD in families of 118 subjects with this disorder enrolled in The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The parental generation included 24 subjects with dementia. Using the Cox proportional hazards model, we found the age-adjusted mother-to-father relative risk to be 2.8 (95% CI, 1.1 to 7.7). Among a subset of 10 families with one affected parent and at least two affected siblings, the ratio of affected mothers-to-fathers was 9:1. These findings support recent studies that found a high mother-to-father ratio among affected parents of subjects with AD. Together, these results suggest maternal inheritance of AD and are consistent with several hypotheses regarding the genetic nature of AD.