Aging and Alzheimer's disease in Down syndrome: Clinical and pathological changes

In this article, we present a clinical description of Alzheimer's disease, review extant literature regarding the prevalence of dementia of the Alzheimer's type in people with Down syndrome, and discuss the relationship between Alzheimer's-type neuropathology and Alzheimer's type dementia in people with Down syndrome. After reaching the age of 30 years, virtually all adults with Down syndrome develop beta-amyloid plaques and tangles, the neuropathological changes of Alzheimer disease. However, substantially fewer than 100% of these adults develop dementia of the Alzheimer's type. When adults with Down syndrome do develop dementia of the Alzheimer's type, it typically does not occur until they are over 50 years of age, a full 15 to 20 years after the inferred development of the neuropathology. This discrepancy may be explained by subtleties in the characteristics of the neuropathology (such as the types and distributions of beta-amyloid plaques and the densities and distributions of neurofibrillary tangles). One variable that may affect the overall neuropathological picture is the type of apo-E allele on chromosome 19. Finally, given the considerable range of individual differences in both neuropathological and clinical expression of Alzheimer's disease, it is possible that as-yet-unidentified aging genes are located on chromosome 21 and influence the rate of precocious aging. These genes may be of greater importance in the clinical expression of Alzheimer's disease than is the triplication of the beta-amyloid gene, which also is located on chromosome 21. © 1996 Wiley-Liss, Inc.