Deficiency in mural vascular cells coincides with blood-brain barrier disruption in alzheimer's disease

Jesse D. Sengillo, Ethan A. Winkler, Corey T. Walker, John S. Sullivan, Mahlon Johnson, Berislav V. Zlokovic

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Neurovascular dysfunction contributes to Alzheimer's disease (AD). Cerebrovascular abnormalities and blood-brain barrier (BBB) damage have been shown in AD. The BBB dysfunction can lead to leakage of potentially neurotoxic plasma components in brain that may contribute to neuronal injury. Pericytes are integral in maintaining the BBB integrity. Pericyte-deficient mice develop a chronic BBB damage preceding neuronal injury. Moreover, loss of pericytes was associated with BBB breakdown in patients with amyotrophic lateral sclerosis. Here, we demonstrate a decrease in mural vascular cells in AD, and show that pericyte number and coverage in the cortex and hippocampus of AD subjects compared with neurologically intact controls are reduced by 59% and 60% (P < 0.01), and 32% and 33% (P < 0.01), respectively. An increase in extravascular immunoglobulin G (IgG) and fibrin deposition correlated with reductions in pericyte coverage in AD cases compared with controls; the Pearson's correlation coefficient r for the magnitude of BBB breakdown to IgG and fibrin vs. reduction in pericyte coverage was -0.96 (P < 0.01) and -0.81 (P < 0.01) in the cortex, respectively, and -0.86 (P < 0.01) and -0.98 (P < 0.01) in the hippocampus, respectively. Thus, deficiency in mural vascular cells may contribute to disrupted vascular barrier properties and resultant neuronal dysfunction during AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)303-310
Number of pages8
JournalBrain Pathology
Volume23
Issue number3
DOIs
StatePublished - May 1 2013

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Pericytes
Blood-Brain Barrier
Blood Vessels
Alzheimer Disease
Fibrin
Hippocampus
Immunoglobulin G
Wounds and Injuries
Amyotrophic Lateral Sclerosis
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Sengillo, J. D., Winkler, E. A., Walker, C. T., Sullivan, J. S., Johnson, M., & Zlokovic, B. V. (2013). Deficiency in mural vascular cells coincides with blood-brain barrier disruption in alzheimer's disease. Brain Pathology, 23(3), 303-310. https://doi.org/10.1111/bpa.12004

Deficiency in mural vascular cells coincides with blood-brain barrier disruption in alzheimer's disease. / Sengillo, Jesse D.; Winkler, Ethan A.; Walker, Corey T.; Sullivan, John S.; Johnson, Mahlon; Zlokovic, Berislav V.

In: Brain Pathology, Vol. 23, No. 3, 01.05.2013, p. 303-310.

Research output: Contribution to journalArticle

Sengillo, Jesse D. ; Winkler, Ethan A. ; Walker, Corey T. ; Sullivan, John S. ; Johnson, Mahlon ; Zlokovic, Berislav V. / Deficiency in mural vascular cells coincides with blood-brain barrier disruption in alzheimer's disease. In: Brain Pathology. 2013 ; Vol. 23, No. 3. pp. 303-310.
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