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 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.
Ohm
T G
TG
Zentrum der Morphologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Kirca
M
M
Bohl
J
J
Scharnagl
H
H
Gross
W
W
März
W
W
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D002888:Chromosomes, Human, Pair 19; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D011110:Polymorphism, Genetic; D012044:Regression Analysis
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E