Several lines of evidence suggest that neurotoxic 3A4 amyloid deposits are of prime importance in the pathogenesis of Alzheimer's disease. Epidemiologically determined risk factors such as Down's syndrome, head injury and apoE allelic status can be explained on the basis of this hypothesis. However, there are difficulties with the hypothesis —amyloid accumulation may be necessary, but is not sufficient to produce the neuronal damage seen in Alzheimer's disease. The association between aluminium exposure and Alzheimer's disease remains unproven and is considered to be increasingly peripheral to recent developments in our understanding of the disease.