Identification in immunolocalization of a new class of proteoglycan (keratan sulfate) to the neuritic plaques of Alzheimer's disease

Abstract

Previous studies have demonstrated three distinct classes of proteoglycans (PGs)/glycosaminoglycans (GAGs) localized to the characteristic lesions (i.e., neuritic plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles) of Alzheimer's disease (AD). These include heparan sulfate (i.e., perlecan), dermatan sulfate (i.e., decorin), and chondroitin sulfate PGs/GAGs. In the present study, two different antibodies demonstrated the presence of a new class of PG (i.e., keratan sulfate) in the neuritic plaques of AD. Asynaptic vesicle keratan sulfate PG (known as SV2PG) was detected by the monoclonal antibodies, anti-SV2 and anti-SV4, which recognize the keratan sulfate core protein and GAG chains, of the SV2PG antigen, respectively. Both antibodies immunolocalized SV2PG primarily to synapses and to dystrophic neurites within neuritic plaques of AD and normal aged brain. The SV2PG was not immunolocalized to diffuse plaques, cerebrovascular amyloid deposits, or neurofibrillary tangles in AD or normal aged brain. SV2PG immunoreactivity in AD brain was similar in distribution to synaptophysin and showed apparent reduced immunoreactiviy+in AD cortex in comparison to age-matched controls. In conjunction with previous studies, these results now suggest that within the neuritic plaques of AD, there are at least four different classes of PGs present. Although heparan sulfate PGs are still the only class of PG immunolocalized to amyloid fibrils within the neuritic plaques of AD, the specific immunolocalization of keratan sulfate, dermatan sulfate, and chondroitin sulfate containing PGs to the periphery of plaques, suggests that these particular PGs/GAGs may also play distinct and important roles in neuritic plaque pathogenesis.