The Role of Telomerase Protein TERT in Alzheimer's Disease and in Tau-Related PathologyIn Vitro

The telomerase reverse transcriptase protein TERT has recently been demonstrated to have a variety of functions bothin vitroandin vivo, which are distinct from its canonical role in telomere extension. In different cellular systems, TERT protein has been shown to be protective through its interaction with mitochondria. TERT has previously been found in rodent neurons, and we hypothesize that it might have a protective function in adult human brain. Here, we investigated the expression of TERT at different stages of Alzheimer's disease pathology (Braak Stages I-VI)in situand the ability of TERT to protect against oxidative damage in anin vitromodel of tau pathology. Our data reveal that TERT is expressedin vitroin mouse neurons and microglia, andin vivoin the cytoplasm of mature human hippocampal neurons and activated microglia, but is absent from astrocytes. Intriguingly, hippocampal neurons expressing TERT did not contain hyperphosphorylated tau. Vice versa, neurons that expressed high levels of pathological tau did not appear to express TERT protein. TERT protein colocalized with mitochondria in the hippocampus of Alzheimer's disease brains (Braak Stage VI), as well as in cultured neurons under conditions of oxidative stress. Ourin vitrodata suggest that the absence of TERT increases ROS generation and oxidative damage in neurons induced by pathological tau. Together, our findings suggest that TERT protein persists in neurons of the adult human brain, where it may have a protective role against tau pathology.