Linkage analysis for plasma amyloid beta levels in persons with hypertension implicates Aβ-40 levels to presenilin 2

Hum Genet. 2012 Dec;131(12):1869-76. doi: 10.1007/s00439-012-1210-2. Epub 2012 Aug 8.


Plasma concentrations of Aβ40 and Aβ42 rise with age and are increased in people with mutations that cause early-onset Alzheimer's disease (AD). Amyloid beta (Aβ) plasma levels were successfully used as an (endo)phenotype for gene discovery using a linkage approach in families with dominant forms of disease. Here, we searched for loci involved in Aβ plasma levels in a series of non-demented patients with hypertension in the Erasmus Rucphen Family study. Aβ40 and Aβ42 levels were determined in 125 subjects with severe hypertension. All patients were genotyped with a 6,000 single nucleotide polymorphisms (SNPs) illumina array designed for linkage analysis. We conducted linkage analysis of plasma Aβ levels. None of the linkage analyses yielded genome-wide significant logarithm of odds (LOD) score over 3.3, but there was suggestive evidence for linkage (LOD > 1.9) for two regions: 1q41 (LOD = 2.07) and 11q14.3 (LOD = 2.97), both for Aβ40. These regions were followed up with association analysis in the study subjects and in 320 subjects from a population-based cohort. For the Aβ40 region on chromosome 1, association of several SNPs was observed at the presenilin 2 gene (PSEN2) (p = 2.58 × 10(-4) for rs6703170). On chromosome 11q14-21, we found some association (p = 3.1 × 10(-3) for rs2514299). This linkage study of plasma concentrations of Aβ40 and Aβ42 yielded two suggestive regions, of which one points toward a known locus for familial AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / genetics*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 11 / genetics
  • Cohort Studies
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / blood*
  • Hypertension / genetics*
  • Lod Score
  • Male
  • Middle Aged
  • Netherlands
  • Peptide Fragments / blood*
  • Peptide Fragments / genetics*
  • Polymorphism, Single Nucleotide
  • Presenilin-2 / genetics*


  • Amyloid beta-Peptides
  • PSEN2 protein, human
  • Peptide Fragments
  • Presenilin-2
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)