Palmitoylethanolamide (PEA) has been emerging as a safe and well tolerated analgesic, anti-inflammatory
and neuroprotective mediator, acting at several molecular targets in the nervous
system. PEA is present in foods, as egg yolk, corn, peanut and soy oil. It is synthesized from lipid
components of cellular membranes and can be found in high concentrations in brain tissues. In
this study, we evaluated the effects of a chronic (6 months) administration of ultra-micronized
PEA on cognitive decline in transgenic Tg2576 (Tg) mice expressing mutant APP. When aged,
Tg mice develop accumulation of amyloid peptide and amyloid plaques in the brain, as well as
cognitive deficits, representing thus an animal model of AD. PEA administration was performed
via a subcutaneous delivery system in Tg mice and wild-type control group (from 6 to 12 months
of age). PEA effects on behavior were observed longitudinally in a pre-symptomatic phase (3
months), a mild-symptomatic phase (6.5 months) and a full-symptomatic phase (11-12 months).
Behavioral assessment was performed by using the following validated tests: Elevated Plus
Maze, Rotarod Test, Y-Maze Spontaneous Alternation Test, Novel Object Recognition Test, Tail
Suspension Test and Morris Water Maze. PEA administration restored the novelty recognition
memory of Tg mice during the full-symptomatic phase. PEA was able to counteract hippocampal-
dependent mnesic deficits, suggesting the therapeutic potential for the early treatment of
AD. Further in progress analyses involve histological evaluation of dendritic branching, spine
number, amyloid plaques and glial reactivity in the hippocampal CA1. This research is aimed
to increase knowledge of the effects of PEA as a safe and low-cost nutraceutical tool useful to
improve quality of life in AD
