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Cerebrovascular Hypoperfusion: A Risk Factor for Alzheimer's Disease?
Author(s) -
JONG G. I.,
VOS R. A. I.,
STEUR E. N. H. JANSEN,
LUITEN P. G. M.
Publication year - 1997
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1997.tb48461.x
Subject(s) - pathology , cerebral cortex , medicine , basement membrane , alzheimer's disease , blood–brain barrier , disease , central nervous system
Although cognitive impairment during aging is usually associated with neuronal alterations, the cerebrovascular system undergoes prominent alterations in aging as well. Using electron microscopy we previously showed a progressive deterioration of the capillary wall in the cerebral cortex of aged rats. In aged rats the capillary basement membrane (BM) is thickened, massive bundles of collagen fibrils are deposited within the BM, and pericytes are degenerating. A compromized cerebrai circulation (e.g., in rats with chronic hypertension) is characterized by an increased number of capillary alterations. In autopsy material (gray matter, gyrus cinguli) of carefully diagnosed patient groups (controls, AD, Lewy body disease, MID and demented Lewy body disease patients) we observed significantly more morphological changes in the capillary bed of demented versus non‐demented patients. In both animal and human material morphological evidence points to a relation between energy‐dependent nutrient transport across the blood–brain barrier and the ultrastructural deviations. In the AD cases we did not find a correlation between the stage of the disease (Braak I‐VI) and the incidence of capillary aberrations, which indicates that the capillary alterations are not a consequence of AD pathology. Simultaneously, we are conducting animal model studies to determine the effects of cerebral hypoperfusion in the rat. Permanent bilateral occlusion of the carotid arteries shifts the behavioral profile of the rats (Morris maze, open field) towards that of aged rats, while the sensitivity for muscarinic ligand agents is altered.