• Alzheimer's disease (AD);
  • elimination;
  • Aβ;
  • cerebrovascular disease (CVD);
  • therapy;
  • aging;
  • brain

Abstract: Alzheimer's disease (AD) is characterized by the intracellular deposition of ubiquitinated tau and by the extracellular accumulation of soluble, insoluble, and fibrillary Aβ. Previous studies suggest that Aβ is normally eliminated from the brain along perivascular pathways that may become blocked in the aging brain, resulting in cerebral amyloid angiopathy. As age is a major risk factor for AD and for cerebrovascular disease (CVD), we test the hypothesis that CVD inhibits the elimination of Aβ from the aging human brain. Sections from 100 aged and AD brains were stained for Aβ by immunohistochemistry and by reticulin and Masson trichrome techniques. Early deposition of Aβ in brain parenchyma was related to individual arterial territories in the cortex. In areas of more extensive accumulation of Aβ, there was an inverse relationship between capillary amyloid angiopathy and plaques of Aβ. Thus, arterial territories with extensive capillary amyloid angiopathy were devoid of Aβ plaques, whereas in areas with abundant diffuse plaques there was no capillary amyloid angiopathy. Serial sections showed that cortical arteries feeding capillary beds with Aβ angiopathy were occluded by thrombus. We conclude that CVD inhibits the elimination of Aβ along capillary walls and changes the distribution of Aβ in the cerebral cortex. Loss of pulsations in thrombosed or arteriosclerotic arteries may thus abolish the motive force necessary for the drainage of Aβ and inhibit the elimination of Aβ. Therapies to increase elimination of Aβ in AD need to consider the effects of CVD on the elimination of Aβ from the aging human brain.