Amyloid Angiopathy and Blood–Brain Barrier Changes in Alzheimer's Disease^a,b

Abstract

Evidence is accumulating that suggests that increased permeability of the BBB to blood-borne proteins is favorable for the development of neuropathologic changes such as amyloid angiopathy and formation of amyloid plaques in the AD brain. To study this problem, we applied a quantitative immunocytochemical procedure that enables evaluation of the barrier function of brain microvasculature to endogenous albumin. This procedure was successfully used on scrapie-infected mice, which represent a unique animal model enabling study of an interrelation between BBB function and deposition of amyloid within vascular wall and neuritic plaques. Biopsy specimens obtained during neurosurgical procedures (tumors and dementia) were also examined. Our observations indicate that (1) the vast majority of brain microvessels in scrapie-infected mice and in demented individuals show normal features of the BBB; (2) only those microvascular segments directly surrounded by amyloid plaques or representing amyloid angiopathy show increased permeability to endogenous albumin; (3) numerous immunosignals over the amyloid deposits in plaques and in the wall of angiopathic vessels suggest the affinity of extravasated albumin to the amyloid material.

Amyloid-Peptide Vaccinations Reduce β-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer’s Transgenic Mice

“…[51][52][53] To examine whether there was any microvascular deposition of A␤ in the retina, that is, retinal amyloid angiopathy, of AD transgenic mice, cross-retinal sections were dual-labeled with both BAM01 and a rabbit polyclonal IgG for vWF, an endothelial cell marker of microvessels. Both A␤ and vWF double-labeled microvessels were quantified and used as retinal amyloid angiopathy scores.…”

Protection of the Blood-Brain Barrier by Pentosan Against Amyloid-β-Induced Toxicity

“…The morphological changes are accompanied by functional alterations, microvascular segments directly surrounded by amyloid plaques or representing cerebral amyloid angiopathy show increased permeability to endogenous albumin [46]. The degree of AD can influence these changes: in mild dementia the integrity of the BBB can be well preserved, while it is disturbed in a graded manner according to the progression of dementia [47].…”

Endothelial cell dysfunction in response to intracellular overexpression of amyloid precursor protein

“…Damage to both endothelial and smooth muscle cells of the vasculature has been reported in CAA (Kalaria and Hedera, 1995;Wisniewski et al, 1997). Overexpression of APP and increased levels of A␤ have been detected in the vasculature in the vicinity of amyloid plaques deposits (Kawai et al, 1993;Tagliavini et al, 1990).…”