Low prevalence of apolipoprotein E ε4 allele in the neurofibrillary tangle predominant form of senile dementia

Abstract

Apolipoprotein E (apoE) genotypes were analyzed in a subset of demented very old patients who share a uniform neuropathological picture consisting of various numbers of neurofibrillary tangles (NFT) in allocortical areas of the inferomedial temporal lobe without significant numbers of either diffuse amyloid or neuritic plaques. Among 18 patients with this condition referred to as NFT-predominant senile dementia (average age at death 87 ± 4.7 years), we found allele frequencies of 0.11 ɛ2, 0.86 ɛ3 and 0.03 ɛ4, which are significantly different from allele frequencies reported in Alzheimer’s disease (0.04 ɛ2, 0.59 ɛ3 and 0.38 ɛ4). The low prevalence of the apoE ɛ4 allele in this subset of patients is striking and suggests that NFT-predominant senile dementia is a dementing neurodegenerative disease in which the deposition of Aβ-amyloid did not occur, possibly due to protective effects of ɛ2 and/or ɛ3 alleles or lack of a promoting effect of apoE ɛ4 on amyloidogenesis. We propose that NFT-predominant dementia is a variant of Alzheimer’s disease occurring in the very old.