The effect of apolipoprotein E genotype on expression of an autosomal dominant schizophreniform disorder with progressive dementia and neurofibrillary tangles

with The apolipoprotein E (APOE) ε4 allele is associated with an increased and the ε2 allele a decreased risk for Alzheimerʹs disease (AD). It has been hypothesized that these risks are mediated by differential effects of the APOE alleles on the cytoskeletal degeneration, which results in neurofibrillary tangle (NFT) formation. It has also been suggested that APOE alleles differentially affect the beta amyloid accumulation. We examined APOE genotypes and their effects on age of onset in a family with an autosomal dominant “neurofibrillary tangle only” dementia. This disorder is manifested by schizophreniform psychosis followed by progressive dementia and neuropathologically by prominent AD-like neurofibrillary tangles without neuritic plaques. The only affected ε4 heterozygote in this family did not demonstrate accelerated disease onset. In contrast, the affected ε2 heterozygote had the latest age of onset of any affected family member. The two other ε2 heterozygotes remained unaffected at an age much greater than the mean age of onset for the disease. These results are consistent with a protective effect of the ε2 allele in a hereditary neuropsychiatric disorder prominent NFT formation.