Effect of palmitoylethanolamide in a triple transgenic model of Alzheimer’s disease

Alzheimer's disease (AD) is a neurodegenerative disorder whose main features are β-amyloid (Aβ) plaques and neurofibrillary tangles, both responsible for neuronal loss and synapses reduction. Recently, the focus of research shifted from a neurocentric point of view to consider the role of non-neuronal cells in promoting disease progression; this is because a continuous astrocyte activation named "reactive gliosis" is seen in AD brain. Many models are developed to reproduce at best the hallmarks of AD and one of these is the 3xTg-AD. Aim of the study was to investigate any differences in the expression of the principal astrocyte activation markers (GFAP and S100β) in 3xTg-AD mice, in comparison with Non-Tg ones, and later evaluate the action of palmitoylethanolamide (PEA). PEA is an endogenous lipidic compound with well known anti-inflammatory properties, mainly produced by glial cells in the central nervous system. We found an increased 3xTg-AD-astrocytes activation compared to Non-Tg, imputable to an increased GFAP expression. PEA was able to control reactive gliosis, bringing cell's functionality to a physiological state. These results strongly suggest that PEA could be a promising tool in the therapeutic strategy against AD.