A relationship between the microvasculature and Alzheimer senile plaques has been suggested by several lines of evidence. Besides close anatomic and biochemical relationships, both extrinsic (fibronectin) and intrinsic [heparan sulfate proteoglycan (HSPG)] components of the vascular basement membrane (VBM) have been colonized with amyloid plaques. The present study was designed to examine the association between three intrinsic components of the VBM [HSPG, collagen type IV (CIV), and laminin] and the histopathologic lesions of Alzheimer's disease (AD). Six cases with neuropathologically confirmed AD were immunocytochemically labeled for the presence of HSPG, CIV, laminin, or tau-2 (a marker for degenerating neurites) and examined at the light and electron microscopic levels. For light microscopic analyses, sections were counterstained with a fluorescent marker for amyloid. The present study illustrates an involvement of VBM components in the lesions associated with AD. First, we replicate our previous finding that HSPG antibodies immunolabel a subset of neurons; ultrastructural analyses indicate that at least some of these are actually extracellular neurofibrillary tangles. Second, we report that CIV and laminin immunoreaction product was not associated with neurons but did label several perivascular cells with the morphologic characteristics of microglia. Finally, we demonstrate that all three intrinsic VBM components, CIV and laminin as well as HSPG, are localized to senile plaques. Both light and electron microscopic studies indicate that the VBM components are associated with amyloid rather than degenerating neurites. These findings suggest that the VBM or its components may play a role in the AD pathogenetic cascade.