Tellurium-based immunomodulating compound SAS inhibits the progression of early-onset Alzheimer`s disease in the 5xFAD mouse model.

Objectives. Alzheimer’s disease (AD) is a progressive incurable neurodegenerative disorder. To date, therapies suggested to be beneficial for AD, are clinically tested at an advanced age, after disease onset. AD is characterized by an overload of amyloid-beta (Aβ) plaque in the central nervous system (CNS); the functional decline correlates with the deposition of Aβ peptide containing plaques, hence clearance of Aβ from the brain is an important therapeutic strategy for Alzheimer`s disease. Previous studies in our lab showed the ability of tellurium compounds to inhibit PD-L1 expression, IL-10, caspase-1, and caspase-3 activities, which were associated with decreased neuronal death, inhibition of IL-1β and up-regulation of GDNF. These results led us to examine the ability of the small organotellurium compound octa-O-bis-(R, R)-tartrate ditelluride (SAS) to reduce Aβ deposits and ameliorate cognitive deficits.

Methods. 5xFAD mice were administered with SAS every other day. Aβ plaques were quantified using immunohistochemistry, cognitive and behavioral abilities were assessed using behavioral paradigms.

Results. Administration of SAS has shown a significant effect of Aβ clearance in the cortex of 5xFAD mice in 5 and 9m of age. 5xFAD/SAS mice exhibit normalized exploratory behavior, along with the alleviation of short-term memory deficits compared with non-treated controls 5xFAD/PBS. This results suggesting that early treatment with SAS may inhibit the progression of AD pathology. We hypothesized that possible mechanism of action is by inhibition of PD-L1 expression and pro-inflammatory cytokine secretion, a process that eventually leads to elevation of neuroprotective factors, nowadays we try to find a possible mechanism of action.

Conclusions. SAS confers long-term beneficial effects in mice, possibly by downregulation of inflammatory cytokines and elevation of neuroprotective factors, resulting in Aβ-clearance and amelioration of cognitive deficits.