Down's syndrome and Alzheimer's dementia: defining an association.
The typical neuropathological features of Alzheimer's disease, plaques and tangles, appear in virtually all patients with Down's Syndrome after the age of 40. Clinically, changes in cognitive performance and behavior appear to correlate with these neuropathological changes, although a satisfactory operational definition of dementia in a context of mental retardation is not available. It is unknown whether the cholinergic losses in the nucleus basalis, which are a feature of early onset Alzheimer's disease, also occur late in Down's syndrome. Two family studies have supported a greater than expected incidence of Down's cases among relatives of probands dying with Alzheimer-type dementia, but the association is not strong. It is noteworthy that in both studies, phenotypically normal carriers of the rare 15/21 translocation had severe early onset dementia, although this translocation is responsible for less than 0.4 per cent of Down's cases. An increased incidence of dementia among carriers of the more common 14/21 translocation has not been reported. In any case, it is proposed that a gene product originating from the long arm of chromosome 21 (21q) is necessary for Alzheimer-type pathology, since a segregating gene could not be responsible for the 100 per cent incidence of these changes among 21q trisomics.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002648:Child; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011950:Receptors, Cholinergic / Q000502:physiology; D014178:Translocation, Genetic
D011950:Receptors, Cholinergic; D002795:Choline O-Acetyltransferase