Age-dependent decline of blood-brain barrier P-glycoprotein expression in the canine brain

Neurobiol Aging. 2011 Aug;32(8):1477-85. doi: 10.1016/j.neurobiolaging.2009.08.014. Epub 2009 Oct 16.


The efflux transporter P-glycoprotein serves as a major molecular gatekeeper at the blood-brain barrier. It has been suggested that a reduction of P-glycoprotein activity with aging might enhance exposure of brain tissue to exogenous and endogenous compounds thereby contributing to the development of neurodegenerative diseases. Brain tissue from owner-kept dogs renders an excellent tool to study the impact of aging on the background of variable environmental and genetic influencing factors. Therefore, we determined expression rates of P-glycoprotein in canine post-mortem tissue from 23 non-laboratory dogs. P-glycoprotein expression in the parahippocampal cortex exhibited a negative correlation with age. Analysis of the area labeled for P-glycoprotein in dogs aged >100 months revealed a 72% drop in P-glycoprotein expression as compared to young adults aged 23-36 months. Respective data from the dentate hilus and dentate gyrus indicated an earlier drop with a reduction by 77 and 80% in dogs aged 37-99 months in comparison with younger individuals. In contrast to the decline observed with aging in dogs without plaques, P-glycoprotein expression rates rather tended to increase with further aging in dogs with plaque formation. In conclusion, the thorough analysis of P-glycoprotein expression rates in non-laboratory dogs revealed a significant decline with aging. The data strongly support the concept that age-dependent changes might predispose to neurodegenerative diseases. In the early pathogenesis of Alzheimer's disease which is modelled by diffuse plaques in the canine brain, an up-regulation of P-glycoprotein might act as a compensatory mechanism to enhance Abeta efflux from the brain. Future studies are necessary to further evaluate the correlation between Abeta deposits and P-glycoprotein expression in different phases of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Aging / pathology
  • Aging / physiology*
  • Amyloidosis / metabolism
  • Amyloidosis / pathology
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain / blood supply*
  • Brain / metabolism*
  • Dogs
  • Female
  • Male
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / physiopathology
  • Up-Regulation / physiology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1