LOW-PREVALENCE OF APOLIPOPROTEIN-E EPSILON-4 ALLELE IN THE NEUROFIBRILLARY TANGLE PREDOMINANT FORM OF SENILE DEMENTIA

Apolipoprotein E (apoE) genotypes were analyzed in a subset of demente d very old patients who share a uniform neuropathological picture cons isting of various numbers of neurofibrillary tangles (NFT) in allocort ical areas of the inferomedial temporal lobe without significant numbe rs of either diffuse amyloid or neuritic plaques. Among 18 patients wi th this condition referred to as NFT-predominant senile dementia (aver age age at death 87 +/- 4.7 years), we found allele frequencies of 0.1 1 epsilon 2, 0.86 epsilon 3 and 0.03 epsilon 4, which are significantl y different from allele frequencies reported in Alzheimer's disease (0 .04 epsilon 2, 0.59 epsilon 3 and 0.38 epsilon 4). The low prevalence of the apoE epsilon 4 allele in this subset of patients is striking an d suggests that NFT-predominant senile dementia is a dementing neurode generative disease in which the deposition of A beta-amyloid did not o ccur, possibly due to protective effects of epsilon 2 and/or epsilon 3 alleles or lack of a promoting effect of apoE epsilon 4 on amyloidoge nesis. We propose that NFT-predominant dementia is a variant of Alzhei mer's disease occurring in the very old.