Localization of amyloid P component in human brain: vascular staining patterns and association with Alzheimer's...

Amyloid P component is a normal serum protein that is highly conserved across phylogeny. Although it resembles the classic acute-phase reactant C-reactive protein, and is considered to be a normal extracellular matrix component, its physiologic role in humans is unknown. Amyloid P component is also colocalized with accumulations of all recognized forms of amyloid. The present study uses light and electron microscopy to compare the cerebral localization of amyloid P component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD). In non-AD cases, amyloid P component was predominantly localized to the cerebrovasculature. Perivascular staining was observed in most cases, more so in the white than in the gray matter. In AD cases, amyloid P component was localized to all three characteristics histopathologic lesions, namely, neurofibrillary tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with prominent staining of gray matter parenchymal lesions, intravascular staining was decreased. Given the fixation and processing methods used, amyloid P component was never seen to be localized to the cerebrovascular basement membrane. These data argue against amyloid P component's postulated role as the anchor for vascular beta-amyloid deposition. Because there is no evidence for intrinsic amyloid P component production in brain, its perivascular and parenchymal distributions suggest either compromise of the blood-brain barrier or transport across vascular endothelium.