LRP1 Expression in Cerebral Cortex, Choroid Plexus and Meningeal Blood Vessels: Relationship to Cerebral Amyloid Angiopathy and APOE Status

Neurosci Lett. 2012 Sep 13;525(2):123-8. doi: 10.1016/j.neulet.2012.07.065.

Abstract

APOE genotype is a risk factor for Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The risk and severity of CAA increase with possession of APOE ε4, whereas APOE ε2 increases the risk of vessel rupture. Uptake of Aβ by cerebrovascular smooth muscle cells (CVSMCs) is mediated by low-density lipoprotein receptor-related protein-1 (LRP1). To determine whether APOE influences CAA by altering LRP1 expression, particularly by CVSMCs, we analysed APOE genotype, CAA severity, and LRP1 levels in post-mortem cerebral cortex, choroid plexus and meningeal vessels. LRP1 mRNA and protein were not related to CAA severity and presence. LRP1 mRNA was increased in meningeal vessels, but not cortex or choroid plexus, in AD and in association with APOE ε4, and was decreased in association with APOE ε3. In brains with CAA, APOE ε2 was associated with decreased LRP1 protein in meningeal vessels, and ε3 with increased LRP1 in choroid plexus. These findings suggest that APOE may influence the severity of CAA through altered expression of LRP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Apolipoproteins E / metabolism*
  • Case-Control Studies
  • Cerebral Amyloid Angiopathy / metabolism*
  • Cerebral Amyloid Angiopathy / pathology
  • Cerebral Cortex / metabolism*
  • Choroid Plexus / metabolism*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Meninges / blood supply*
  • RNA, Messenger / metabolism

Substances

  • Apolipoproteins E
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • RNA, Messenger