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Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders

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Abstract

Alterations of the cerebral microvasculature have been reported in aging and in neurodegenerative disorders such as Alzheimer's disease. However, the exact role of microvascular alterations in the pathogenesis of neurodegeneration remains unknown. In the present report, the cerebral cortex microvasculature was studied by immunohistochemistry using a monoclonal antibody against vascular heparan sulfate proteoglycan protein core in normal aging controls, Alzheimer's disease, Down syndrome, Guam amyotrophic lateral sclerosis/parkinsonian dementia complex, Pick's disease and dementia pugilistica. In all dementing illnesses, increased microvascular pathology was evident compared to normal controls. Decreased microvascular density and numerous atrophic vessels were the primary abnormalities observed in all dementing disorders. These microvascular abnormalities demonstrated regional and laminar selectivity, and were primarly found in layers III and V of frontal and temporal cortex. Quantitative analysis employing computer-assisted microscopy demonstrated that the decrease in microvascular density in Alzheimer's disease was statistically significant compared to age-matched controls. In addition, extracellular heparan sulfate proteoglycan deposits were observed which colocalized with thioflavine S-positive senile plaques in Alzheimer's disease, Down syndrome and selected Guam dementia cases. In some cases, heparan sulfate proteoglycan was seen in senile plaques that appeared to be diffuse or primitive plaques that stained weakly with thioflavine. Heparan sulfate proteoglycan-containing neurons were also observed in Alzheimer's disease, as well as in Down syndrome and Guam cases. Glial staining for heparan sulfate proteoglycan was never observed. Our data support previous observations that microvascular pathology is found in aging and in Alzheimer's disease. The changes in Alzheimer's disease exceed those found in normal aging controls. We also found microvascular pathology in all other dementing disorders studied. Our studies further demonstrated that the microvascular pathology displays regional and laminar patterns which parallel patterns of neuronal loss. Finally, we also found that heparan sulfate proteoglycan is present in senile plaques and neurons not only as previously reported in Alzheimer's disease, but also in Down syndrome and Guam cases. Heparan sulfate proteoglycan in senile plaques may be derived from either the degenerating microvasculature or from degenerating neurons. Further studies are necessary to determine the role of microvascular disease in the progression of Alzheimer's disease and other dementing disorders.

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Authors and Affiliations

  1. Department of Geriatrics and Adult Development, The Mount Sinai Medical Center, Box 1070, 10029-6574, New York, NY, USA

    L. Buée, P. R. Hof, A. Delacourte, J. H. Morrison & H. M. Fillit

  2. Department of Pathology and Psychiatry, The Mount Sinai Medical Center, 10029-6574, New York, NY, USA

    D. P. Perl

  3. Department of Medicine, The Mount Sinai Medical Center, 10029-6574, New York, NY, USA

    H. M. Fillit

  4. Fishberg Research Center for Neurobiology, The Mount Sinai Medical Center, 10029, New York, NY, USA

    P. R. Hof, C. Bouras, D. P. Perl, J. H. Morrison & H. M. Fillit

  5. Unité 156, INSERM, F-59045, Lille Cédex, France

    L. Buée & A. Delacourte

  6. Département de Psychiatrie, IUPG Bel-Air, Université de Genève, Chene-Bourg, CH-1225, Geneve, Switzerland

    C. Bouras

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  1. L. Buée
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Buée, L., Hof, P.R., Bouras, C. et al. Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders. Acta Neuropathol 87, 469–480 (1994). https://doi.org/10.1007/BF00294173

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  • DOI: https://doi.org/10.1007/BF00294173

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