Cerebrovascular hypoperfusion: A risk factor for Alzheimer's disease? Animal model and postmortem human studies

G.I. de Jong*, R.A.I. de Vos, E.N.H. Jansen Steur, P.G.M. Luiten

*Corresponding author for this work

    Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

    Abstract

    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 compromised cerebral circulation (e.g., in rats with chronic hypertension) is characterized by an increased number of capillary alterations. In autopsy material (gray matter, gyrus cingula) 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.

    Original languageEnglish
    Title of host publicationCerebrovascular Pathology in Alzheimer's Disease
    EditorsJ.C. de la Torre, V. Hachinski
    Place of Publicationnew York
    PublisherNew York Academy of Sciences
    Pages56-74
    Number of pages19
    Volume826
    Edition1
    ISBN (Print)1-57331-087-5
    DOIs
    Publication statusPublished - 1997
    EventConference on Cerebrovascular Pathology in Alzheimers Disease -
    Duration: 12-Nov-199615-Nov-1996

    Publication series

    NameAnnals of the New York Academy of Sciences
    PublisherNEW YORK ACAD SCIENCES
    Volume826
    ISSN (Print)0077-8923

    Other

    OtherConference on Cerebrovascular Pathology in Alzheimers Disease
    Period12/11/199615/11/1996

    Keywords

    • BLOOD-BRAIN-BARRIER
    • AGE-RELATED-CHANGES
    • CEREBRAL-CORTEX
    • AGING RAT
    • GLUCOSE-TRANSPORTER
    • BASEMENT-MEMBRANE
    • CAPILLARIES
    • MICROVASCULATURE
    • PERMEABILITY
    • METABOLISM

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