Neuritic Involvement within bFGf Immunopositive Plaques of Alzheimer's Disease

Abstract

As early as 1928, Cajal suggested that plaques contain a trophic substance which attracts neurites. Recently, basic fibroblast growth factor (bFGF) levels were shown to be elevated in Alzheimer's disease (AD) and localized to plaques and neurofibrillary tangles. We sought to clarify the subtype of plaques which contain bFGF and provide more detail on bFGFs neuronal and vascular localization in normal aged brain, AD brain, and Down's syndrome (DS) brain. We combined double-labeling immunocytochemistry for bFGF with heparan sulfate glycosaminoglycans, β-amyloid, and thioflavine flourescence. In additions, the neuritic markers tau-1 and PHF-1 were combined with bFGF staining. Eleven AD, five nondemented controls, and four DS cases were examined. Most bFGF immunopositive plaques contained numerous dystrophic fibers, indicating they were of the neuritic subtype. We also detected a variety of bFGF-positive cells, including hilar, dentate granule, pyramidal, and stellate neurons, as well as astrocytes. The basements membrane of large and small arterioles also contained bFGF. bFGF immunoreactivity within neurons, astrocytes and the vasculature was increased in AD cases relative to controls. Immunoreactivity within the DS cases was intermediate. These results suggest that bFGF is up-regulated in AD and support the hypothesis that bFGF may attract neurites into plaques. Alternatively, an injured neurite may induce bFGF production by responding glia, resulting in further neuritic attraction.