Gender differences in the phenotypic expression of Alzheimerʼs disease in Downʼs syndrome (Trisomy 21)

Twenty-eight individuals with typical Downʼs syndrome (DS) phenotype (17 males and 11 females; age range10-74 years) were investigated for gender differences in the phenotypic expression of Alzheimer-type pathology (ATP). Quantitative neuropathology was performed in the 4 neocortical lobes of the right hemisphere, by counting senile plaques (SP), and neurofibrillary tangles (NFT). ATP was present in 25 middle-aged (>40 years) individuals (16 males and 9 females). Females had significantly higher (p = 0.03) mean neocortical NFT densities (36.6 per mm; s.e.m. ± 6.6) than males (17.9 per mm; s.e.m. ± 4.7). None of the females had NFT densities below 10 per mm, compared with 6 males in whom NFT were either absent or seen in very low densities (< 4 per mm). Assessment of SP densities in the same cortical regions showed non-significant differences in females (42.4 per mm; s.e.m. ± 5.1) compared with males (33.6 per mm; s.e.m. ± 2.1). There was clinical evidence of dementia in all the female (8/8) individuals who were prospectively assessed, compared with only 54% (7/13) of males. The male individuals without clinical dementia had absent or low neocortical NFT densities regardless of high SP densities. Female DS cases (mean age48.8 years; s.e.m. ± 1.9) had an earlier onset of dementia than males (mean age53.6 years; s.e.m. ± 1.3; p = 0.05). Female middle-aged DS individuals have an earlier onset, and a more severe form of AD which correlates with higher neocortical NFT rather than SP density.