Research article
Increased density of senile plaques (SP), but not neurofibrillary tangles (NFT), in non-demented individuals with the apolipoprotein E4 allele: comparison to confirmed Alzheimer's disease patients

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Abstract

The apolipoprotein E genotype and cortical senile plaque (SP) and cortical and hippocampal neurofibrillary tangle (NFT) densities were determined in non-demented individuals and neuropathologically confirmed AD patients. The non-demented population was further subdivided according to presence or absence of pathologically established critical coronary artery disease (cCAD), hypertension (HyperT), or neither (non-heart disease; non-HD). The apolipoprotein E4 (APOE4) allele incidence and dose frequencies were increased in the AD, cCAD and HyperT groups compared to the non-HD controls. The mean number of SP and NFT was significantly increased with the presence of the APOE4 allele within the entire population. After grouping the non-demented subjects according to cardiac status, SP but not NFT density was increased among those individuals with the APOE4 genotype. In HyperT, the increased density of SP also correlated to the APOE4 allele dose frequency. The density of SP and NFT was increased in all regions of AD brain compared to all other non-demented groups, but no significant difference was found between AD patients with or without an APOE4 allele. These two AD groups were age-matched, but could not be matched for disease duration. The data suggest a relationship between heart disease, APOE4 genotype and the presence of SP regardless of cognitive status.

References (51)

  • M.M. Breteler et al.

    Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam study

    Br Med J

    (1994)
  • E.H. Corder et al.

    Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families

    Science

    (1993)
  • R. Couderc et al.

    Prevalence of apolipoprotein E phenotype in ischemic cerebrovascular disease: A case-control study

    Stroke

    (1993)
  • C. Czech et al.

    Apolipoprotein E-4 gene dose in clinically diagnosed Alzheimer's disease: Prevalence, plasma cholesterol levels and cerebrovascular change

    Eur Arch Psychiatry Clin Neurosci

    (1994)
  • C. Czech et al.

    Lancet

    (1993)
  • J. Davignon et al.

    Apolipoprotein E polymorphism and atherosclerosis

    Arteriosclerosis

    (1988)
  • G.B. Frisoni et al.

    Association of apolipoprotein E4 with vascular dementia

    J. Am. Med. Assoc.

    (1994)
  • R.E. Gregg et al.

    Apolipoprotein E modulates the metabolism of apolipoprotein B containing lipoproteins by multiple mechanisms. Cholesterol Transport Systems and Their Relation to Atherosclerosis

  • R.E. Gregg et al.

    Abnormal in vivo metabolsim of apolipoprotein E4 in Humans

    J Clin Invest

    (1986)
  • Z. Khachaturian

    Diagnosis of Alzheimer's disease

    Arch Neurol

    (1985)
  • H. Kurosawa et al.

    The relationship between mental disorders and physical severities in patients with acute myocardial infarction

    Jpn Circ J

    (1983)
  • J. Kuusisto et al.

    Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: Population based study

    Br Med J

    (1994)
  • A. Lehtonen et al.

    High-density lipoprotein cholesterol levels of very old people in the diagnosis of dementia

    Age Ageing

    (1986)
  • G. Lucotte et al.

    Lancet

    (1993)
  • R.W. Mahley

    Apolipoprotein E: Cholesterol transport protein with expanded role in cell biology

    Science

    (1988)
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