APOLIPOPROTEIN-E POLYMORPHISM INFLUENCES NOT ONLY CEREBRAL SENILE PLAQUE LOAD BUT ALSO ALZHEIMER-TYPE NEUROFIBRILLARY TANGLE FORMATION

Only recently, evidence was provided that apolipoprotein E allele epsi lon 4 located on Chromosome 19 is associated with late onset (i.e. sen ile) sporadic Alzheimer's disease. Histologically, Alzheimer's disease is associated with intraneuronal neurofibrillary changes and extraneu ronal A4/beta-amyloid deposition. We set out with a histological stagi ng system which considers the gradual development of Alzheimer's disea se-related histological changes over time and correlates highly with t he cognitive decline ante mortem. Our analysis revealed that both the mean stage for A4/beta-amyloid deposits and the mean stage for neurofi brillary tangles get significantly shifted upwards in epsilon 4-carrie rs. This represents an earlier onset of the histopathological process of about one decade. The fact that both types of Alzheimer's disease-r elated changes correlate positively with the prevalence of the epsilon 4-allele suggests for a causal relationship between the apolipoprotei n E polymorphism and the development of Alzheimer's disease.