Brain Microvascular Changes in Alzheimer's Disease and Other Dementiasa

Authors


  • a

    This work was supported by INSERM, CNRS, NIH Grant AG05138, and The Brookdale Foundation.

d Addresses for telecommunication: L. Buée: phone, +33 / (0) 320 622074; fax, +33 / (0) 320 622079; e-mail: buee@lille.inserm.fr; P.R. Hof: phone, +1/212 241 1760; fax, +1 / 212 996 9785; e-mail: hof@cortex.neuro.mssm.edu; A. Delacourte: phone, +33 / (0) 320 622078; fax, +33 / (0) 320 622079; e-mail: delacourte@lille.inserm.fr

Abstract

ABSTRACT: Vasculopathy in Alzheimer's disease (AD) may represent an important pathogenetic factor of this disorder. In the present study, microvasculature was studied by immunohistochemistry using a monoclonal antibody against a vascular heparan sulfate proteoglycan. Vascular changes were consistently observed in AD and included decrease in vascular density, presence of atrophic and coiling vessels, and glomerular loop formations. The laminar and regional distribution of these vascular alterations was correlated with the presence of neurofibrillary tangles. However, vascular changes may also follow neuronal loss. Vascular density may be related to a decrease in brain metabolism. Furthermore, one of the main features of AD is the presence of amyloid deposits within brain parenchyma and blood vessel walls. It is not yet clear whether amyloid components are derived from the blood or the central nervous system. Because AD is clearly heterogeneous, based on clinical and genetic data, evidence for either a brain or peripheral origin is discussed. Microvasculature was also analyzed in other neurodegenerative disorders devoid of amyloid deposits including amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam and Pick's disease. In conclusion, if vasculopathy in neurodegenerative disorders is not directly involved in pathogenesis, it may act synergistically with other pathogenetic mechanisms including genetic and environmental factors. This aspect of pathology is particularly interesting in view of its accessibility to therapeutic interventions.

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