A 3 '-UTR polymorphism in the oxidized LDL receptor 1 gene increases A beta(40) load as cerebral amyloid angiopathy in Alzheimer's disease

Jieping Shi, JZ Tian, A Pritchard, Corinne L. Lendon, JC Lambert, T Iwatsubo, David M. A. Mann

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Abstract

It is presently unclear whether polymorphic variations in the oxidized low-density lipoprotein receptor 1 (OLR1), or low-density lipoprotein receptor-related protein 1 (LRP1), genes act as risk factors for Alzheimer’s disease (AD). In the present study, we have investigated the extent of amyloid β protein (Aβ) deposition as cerebral amyloid angiopathy (CAA) or senile plaques (SP) in relationship to OLR1 +1071 and +1073 polymorphisms and LRP1 C766T polymorphism in patients with AD There was an increased Aβ40 load as CAA, but not as SP, in frontal cortex of AD patients carrying OLR1+1073 CC genotype, compared to those with CT, TT or CT+TT genotypes, but only in those individuals without apolipoprotein (APOE) ε4 allele. No differences in total Aβ or Aβ42 load as CAA or SP between OLR1+1073 genotypes was seen, nor were there any differences between OLR1+1071 and LRP1 genotypes for any measure of Aβ. Present data suggests that homozygosity for the C allele for OLR1+1073 polymorphism, selectively in individuals without APOE ε4 allele, may impair clearance of Aβ, and particularly Aβ40, from the brain across the blood-brain barrier, leading to its ‘diversion’ into perivascular drainage channels, thereby increasing the severity of CAA in such persons.
Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalActa Neuropathologica
Volume111
Issue number1
Early online date22 Nov 2005
DOIs
Publication statusPublished - Jan 2006

Keywords

  • Alzheimer's disease
  • OLR1 gene
  • LRP1 gene
  • cerebral amyloid angiopathy
  • amyloid beta protein

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