APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome

Background: Alzheimer disease (AD) neuropathology is present in Down syndro me (DS) after age 35, but dementia onset varies from ages 40 to 70 years. B ecause of small sample sizes and nonuniform determination of dementia, prev ious studies produced differing results on the influence of APOE subtypes o n AD in DS. Objective: To determine the influence of the APOE genotype and gender on development of AD in adults with DS to ascertain similarities wit h AD in the general population. Methods: A total of 100 adults with DS (age s 35 to 79 years), almost all of whom were longitudinally assessed by neuro logists, underwent APOE genotyping. Dementia onset was determined using cri teria applied from the Tenth International Classification of Mental and Beh avioral Disorders. This cohort contains the largest number of DS subjects w ith dementia (n = 57) in a single study, thus increasing reliability of the results. Results, The epsilon 2 allele frequency was 4% in those with deme ntia versus 13% in those without dementia (p = 0.03); epsilon 4 allele freq uency was 18% in those with dementia versus 13% in those without dementia ( p = 0.45), Using APOE-epsilon 3/3 as the reference group, the risk ratio fo r the development of AD at any given time was 0.34 for the APOE-epsilon 2/3 group (p = 0.04) and 1.44 for the APOE-epsilon(3/4,4/4) group (p = 0.25). Women were 1.77 times as likely to dement as men at any given point in time (p = 0.04). Conclusions: The epsilon 2 allele confers a protective effect, and women with DS have an increased risk for AD, as in the general populat ion. In this sample, epsilon 4 does not confer a significantly increased ri sk for AD in DS.