Evidence of angiogenic vessels in Alzheimer's disease

J Neural Transm (Vienna). 2009 May;116(5):587-97. doi: 10.1007/s00702-009-0226-9. Epub 2009 Apr 16.

Abstract

Alterations in the blood brain barrier and brain vasculature may be involved in neurodegeneration and neuroinflammation. We sought to determine if vascular remodeling characterized by angiogenic vessels or increased vascular density, occurred in pathologically confirmed Alzheimer's disease (AD) postmortem human brain tissues. We examined brains of deceased, older catholic clergy from the Religious Order Study, a longitudinal clinical-pathological study of aging and AD. The hippocampus, midfrontal cortex, substantia nigra, globus pallidus and locus ceruleus were examined for integrin alphavbeta3 immunoreactivity, a marker of angiogenesis, and vascular densities. Activated microglia cell counts were also performed. All areas except the globus pallidus exhibited elevated alphavbeta3 immunoreactivity in AD cases compared with controls. Only in the hippocampus did the ongoing angiogenesis result in increased vascular density compared with controls. Vascular density was correlated with Abeta load in the hippocampus and alphavbeta3 reactivity was correlated with neurofibrillary tangles in the midfrontal cortex and in the substantia nigra. These data indicate that ongoing angiogenesis is present in brain regions affected by AD pathology and may be related to tissue injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism
  • Arterioles / metabolism
  • Arterioles / pathology
  • Arterioles / physiopathology
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / physiopathology
  • Brain / blood supply
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Mapping
  • Cell Count
  • Cerebral Arteries / metabolism
  • Cerebral Arteries / pathology*
  • Cerebral Arteries / physiopathology
  • Disease Progression
  • Encephalitis / metabolism
  • Encephalitis / pathology
  • Encephalitis / physiopathology
  • Female
  • Gliosis / metabolism
  • Gliosis / pathology
  • Gliosis / physiopathology
  • Humans
  • Immunohistochemistry
  • Integrin alphaVbeta3 / analysis
  • Integrin alphaVbeta3 / metabolism
  • Male
  • Microcirculation / physiology
  • Microglia / pathology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Pathologic / physiopathology

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Integrin alphaVbeta3

Grants and funding