S100β protein expression in Alzheimer disease: Potential role in the pathogenesis of neuritic plaques

Abstract

Increased synthesis and release of S100β protein from activated astrocytes has been implicated in the overgrowth of dystrophic neurites in neuritic plaques in Alzheimer disease (AD). To evaluate the quantitative relationships between tissues levels of S100β and the numbers of neuritic plaques, by Tau‐2 immunoreactive (Tau‐2⁺) labeling, in tissue sections of hippocampus and adjacent temporal cortex and measured the levels of S100β protein, by Western immunoblot labeling, in samples of analagous regions from contralateral hemisphere of the same patients. In AD, tissue levels of S100β (two‐ to fivefold that of controls) were significantly correlated with the number of Tau‐2⁺ plaques (R = 0.82, P < .01). Dual‐label immunohis‐tochemical analysis showed that most S100β⁺ cells were activated GFAP⁺ astrocytes. These results were substantiated by a significant correlation between S100β and GFAP tissue levels (R = 0.81, P < .05). Many of the S100β⁺ astrocytes were clustered around and within Tau‐2⁺ plaques. Indeed, no Tau‐2⁺ plaques were found without associated activated S100β⁺ astrocytes. Our findings provide further evidence of a role for S100β protein in dysregulation of neurons that leads to apparently nonsensical growth of imperfect neurites in AD, a potential key element in early stages of neuritic plaque pathogeneis.