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Abstract
Only recently, evidence was provided that apolipoprotein E allele epsilon 4 located
on Chromosome 19 is associated with late onset (i.e. senile) sporadic Alzheimer's
disease. Histologically, Alzheimer's disease is associated with intraneuronal neurofibrillary
changes and extraneuronal A4/beta-amyloid deposition. We set out with a histological
staging system which considers the gradual development of Alzheimer's disease-related
histological changes over time and correlates highly with the cognitive decline ante
mortem. Our analysis revealed that both the mean stage for A4/beta-amyloid deposits
and the mean stage for neurofibrillary tangles get significantly shifted upwards in
epsilon 4-carriers. This represents an earlier onset of the histopathological process
of about one decade. The fact that both types of Alzheimer's disease-related changes
correlate positively with the prevalence of the epsilon 4-allele suggests for a causal
relationship between the apolipoprotein E polymorphism and the development of Alzheimer's
disease.