In an extremely interesting article which touched upon early-onset dementia I feel that Dr Holmes (Reference Holmes2002) failed to mention Down's syndrome as being a particular risk factor for the development of early-onset Alzheimer's disease because of triplication of the amyloid precursor gene. It is well known that almost all adults over the age of 40 years with Down's syndrome display Alzheimer's neuropathology (Reference MannMann, 1988) and the prevalence of dementia in people with Down's syndrome is 0-4% under the age of 30 years rising to 29-75% at 60-65 years of age, which falls under the category of early-onset Alzheimer's disease (Reference Zigman, Schupf and HavemanZigmanet al, 1997). Studies have shown that the prevalence of Alzheimer's disease in those with learning disability, especially Down's syndrome, is higher than in those with no learning disability (Reference Patel, Goldberg and MossPatel et al, 1993).

The occurrence of Alzheimer-like neuropathology in Down's syndrome suggests that the genetic defect for familial Alzheimer's disease might reside on chromosome 21, which was, therefore, the first of the 22 autosomes to be tested using a genetic linkage strategy (Reference McGuffin, Owen and O'DonovanMcGuffin et al, 1994).

Dr Holmes's article was published among papers with the overall topic of old age psychiatry; early-onset Alzheimer's disease tends to fall within the remit of old age psychiatry except in those with Down's syndrome, who remain within learning disability services. From all the information I have gathered on Alzheimer's disease I have assumed that the clearest evidence for a genetic contribution to the aetiology of Alzheimer's disease is its association with Down's syndrome, which surely deserves a mention when discussing this specific area.