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Acta Neuropathologica

, Volume 111, Issue 1, pp 15–20 | Cite as

A 3’-UTR polymorphism in the oxidized LDL receptor 1 gene increases Aβ40 load as cerebral amyloid angiopathy in Alzheimer’s disease

  • Jing Shi
  • Jinzhou Tian
  • Antonia Pritchard
  • Corinne Lendon
  • Jean-Charles Lambert
  • Takeshi Iwatsubo
  • David M. A. Mann
Regular Paper

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.

Keywords

Alzheimer’s disease OLR1 gene LRP1 gene Cerebral amyloid angiopathy Amyloid β protein 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Jing Shi
    • 1
    • 2
  • Jinzhou Tian
    • 1
    • 2
  • Antonia Pritchard
    • 3
  • Corinne Lendon
    • 3
  • Jean-Charles Lambert
    • 4
  • Takeshi Iwatsubo
    • 5
  • David M. A. Mann
    • 1
  1. 1.Clinical Neuroscience Research GroupUniversity of Manchester, Hope HospitalSalfordUK
  2. 2.Department of Care of the Elderly, Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina
  3. 3.Molecular Psychiatry, Queen Elizabeth Psychiatry HospitalUniversity of BirminghamBirminghamUK
  4. 4.INSERM 508Institut Pasteur de LilleLilleFrance
  5. 5.Department of NeuropathologyUniversity of TokyoTokyoJapan

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