Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia

Dement Geriatr Cogn Disord. 2004;18(2):189-96. doi: 10.1159/000079200. Epub 2004 Jun 21.

Abstract

Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Apolipoproteins A / blood
  • Apolipoproteins A / genetics
  • Cerebral Infarction / blood
  • Cerebral Infarction / complications
  • Cerebral Infarction / genetics
  • Dementia, Vascular / blood
  • Dementia, Vascular / diagnosis*
  • Dementia, Vascular / genetics
  • Female
  • Gene Frequency / genetics
  • Humans
  • Intracranial Embolism / blood
  • Intracranial Embolism / complications
  • Intracranial Embolism / genetics
  • Italy
  • Lipoprotein(a) / blood*
  • Lipoprotein(a) / genetics
  • Male
  • Molecular Weight
  • Phenotype
  • Polymorphism, Genetic / genetics
  • Protein Isoforms / blood
  • Protein Isoforms / genetics
  • Reference Values
  • Risk Factors

Substances

  • Apolipoproteins A
  • Lipoprotein(a)
  • Protein Isoforms