title: The effect of apolipoprotein E genotype on expression of an autosomal dominant schizophreniform disorder with progressive dementia and neurofibrillary tangles.
abstract: The apolipoprotein E (APOE) epsilon 4 allele is associated with an increased and the epsilon 2 allele a decreased risk for Alzheimer's 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 epsilon 4 heterozygote in this family did not demonstrate accelerated disease onset. In contrast, the affected epsilon 2 heterozygote had the latest age of onset of any affected family member. The two other epsilon 2 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 epsilon 2 allele in a hereditary neuropsychiatric disorder with prominent NFT formation.
authors.affiliation: VA Puget Sound Health Care System, Psychiatry Service, Seattle, WA 98195, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tsuang
authors.forename: M A
authors.initials: MA
authors.lastname: Raskind
authors.forename: J
authors.initials: J
authors.lastname: Leverenz
authors.forename: E R
authors.initials: ER
authors.lastname: Peskind
authors.forename: G
authors.initials: G
authors.lastname: Schellenberg
authors.forename: T D
authors.initials: TD
authors.lastname: Bird
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D005787:Gene Frequency / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D016874:Neurofibrillary Tangles / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011618:Psychotic Disorders / Q000235:genetics* / Q000473:pathology; D012306:Risk
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E