Amyloid and Tau Induce Cell Death Independently of TSPO Polymerization and Density Changes.

Abstract

Apoptosis-dependent cell death of astrocytes has been described in Alzheimer’s disease and is linked to the presence of two markers of the pathology: the β-amyloid peptide (Aβ) and the hyperphosphorylated Tau protein. Astrocytes also show reactive states characterized by the overexpression of the 18 kDa translocator protein (TSPO). However, TSPO is also known, in other areas of research, to participate in cell proliferation and death. Regulation of its function by autopolymerization has been described, but its involvement in apoptosis remains unknown. The aim was to determine the effects of Aβ, Tau, and TSPO antagonists on proliferation/cell death and TSPO polymerization in the C6 astrocytic cell line. The dose-effect on cell death in response to Aβ and Tau was observed but without alterations of TSPO density and polymerization. In contrast, nanomolar doses of antagonists stimulated cell proliferation, although micromolar doses induced cell death with a reduction in TSPO density and an increase in the ratio between the 36 and the 72 kDa TSPO polymers. Therefore, an alteration in the density and polymerization of TSPO appears to be related to cell death induced by TSPO antagonisms. In contrast, Aβ- and Tau-induced death seems to be independent of TSPO alterations. In conclusion, even if its role in cell death and proliferation is demonstrated, TSPO seems to, in the context of Alzheimer’s disease, rather represent a marker of the activity of astrocytes than of cell death.