Astrocytes and Alzheimer’s disease: the pharmacological manipulation as promising tool against pathology progression. Evidence from a triple transgenic model of the disease

Alzheimer's disease (AD) is a serious health and economic challenge. So far, available treatments provide only symptomatic relief, making necessary a multitargeted approach against the several pathological processes underlying such disease. In particular, Aβ- and tau-pathology, astrocyte dysfunction, neuroinflammation and glutamate unbalance are the main targets to counteract. To this aim, palmitoylethanolamide (PEA) can be considered a multitargeted treatment strategy. Here, we tested the effects of a 3-months treatment with ultramicronized PEA (um-PEA) in young (6-month-old) and adult (12-month-old) 3×Tg-AD mice, compared to their age-matched Non-Tg mice. In particular, potential neuropathological mechanisms were assessed by western blot, RT-PCR, and immunofluorescence in the hippocampal tissues. Our finding revealed that um-PEA normalizes astrocytic functionality, rebalances the astrocyte glutamate regulating system, restrains neuroinflammation and promotes neuronal survival. Such um-PEA efficacy is potent especially in younger mice, suggesting its potential as a precocious treatment. Since PEA is already licenced for use in humans, displaying a high tolerability and safety profile, it would be an ideal candidate for a long-term use lasting several years, as potential AD treatment requires.