Microangiopathy and the colocalization of heparan sulfate proteoglycan with amyloid in senile plaques of Alzheimer's disease.
While the pathogenetic mechanisms responsible for Alzheimer's Disease (AD) remain unknown, blood vessel deformities, thickened vascular basement membrane (VBM), and amyloid fibrils emanating from the VBM all suggest vascular involvement. The present study immunocytochemically localized the VBM constituent heparan sulfate proteoglycan (HSPG), which is said to play a role in filtration of anionic and neutral proteins. In addition, thioflavine S was used to double-label each tissue section for the presence of amyloid. Samples were taken from frontal, temporal and parietal lobes of 8 patients who exhibited the neuropathologic lesions of AD and 6 patients who did not. HSPG immunolabeled the capillary bed in all samples. Tissue from patients with AD, however, exhibited severe microangiopathic changes: ragged and irregular outer capillary walls, both thickened and attenuated capillary diameters, and regionally increased capillary density. In addition, plaque-like extravascular accumulations of HSPG were seen in all patients with AD. These accumulations were found in the vicinity of capillaries, and were commonly colocalized with amyloid. Neither extravascular clouds of HSPG immunoreactivity nor fluorescing accumulations of amyloid were found in non-AD patients. The pattern of HSPG immunostaining confirms: (1) the high incidence of microangiopathy in AD; (2) the close anatomic relationship between plaque constituents and capillaries; and (3) the colocalization of HSPG with extravascular amyloid. The cerebral vasculature, and specifically the VBM, may thus be actively involved in the pathogenesis of AD.
Perlmutter
L S
LS
University of Southern California School of Medicine, Department of Neurology, Los Angeles 90033.
Chui
H C
HC
Saperia
D
D
Athanikar
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000686:Amyloidosis / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011509:Proteoglycans / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans