710 West 168th Street, 3rd floor
Our group conducts studies of aging and Alzheimer's disease in adults with Down syndrome, in collaboration with colleagues at the NYS Institute for Basic Research. A major focus of current work is the investigation of genetic and host factors that increase ÃŸ -amyloid load or accelerate the accumulation of fibrillized amyloid plaques. We are examining the relation of these factors to age at onset and risk for Alzheimer's disease. Recent work includes:
Studies of the relationship between estrogen deficiency, indicated by age at onset of menopause, apolipoprotein E genotype and age at onset of Alzheimer's disease in women with Down syndrome. We have shown that onset of dementia is associated with age at menopause in women with Down syndrome, and that this association is independent of APOE genotype. Hormonal studies have found that free or bioavailable estrogen levels, rather than total estrogen levels, are associated with dementia. These findings support a neuroprotective role for estrogen.
Investigation of the relation of plasma amyloid ÃŸ peptides to onset of dementia in adults with Down syndrome. We have shown that AÃŸ1-42 and AÃŸ1-40 levels are significantly higher in adults with DS than in controls from the general population and that AÃŸ1-42 levels are selectively increased in demented adults with DS. An increase in AÃŸ1-42, but not AÃŸ1-40, levels was also found both in nondemented subjects and demented subjects with an APOE e4 allele. These findings support the hypothesis that individual differences in AÃŸ processing, distinct from overexpression of APP, may act as an initial step in the pathogenesis of AD.