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Ultramicronized palmitoylethanolamide restores astrocyte-neuron metabolic coupling and Klotho/FGF21 signaling in a triple-transgenic mouse model of Alzheimer's disease

Roberta Facchinetti, Marta Valenza, Claudia Ciarla, Luca Steardo Jr, Gaetano Serviddio, Gianmauro Palombelli, Alexei Verkhratsky, Luca Steardo, Rossella Canese, Tommaso Cassano, Caterina Scuderi. Biomed Pharmacother. 2026 Feb:195:118965.

Laboratory studyOther animals

Design
Laboratory study
Subjects
Triple-transgenic (3xTg-AD) mice, 6 and 12 months old
Dose used in the study
Not stated in the abstract
Duration
Chronic treatment, assessed at 6 and 12 months of age
What was measured
Brain lactate, glutamate/glutamine and taurine levels by MRI/MRS; FGF21, Klotho and insulin receptor expression; ADAM10/ADAM17 metalloprotease levels, by Western blot, in frontal cortex and hippocampus.

What the authors reported

3xTg-AD mice showed lactate build-up, glutamine/glutamate imbalance, taurine depletion and reduced FGF21, Klotho and insulin receptor expression. Um-PEA treatment rebalanced lactate-glutamate metabolism, increased taurine synthesis and transport, raised FGF21, Klotho and insulin receptor expression, and changed ADAM10 and ADAM17 metalloprotease levels.

Limits of this study

A transgenic mouse model study; it cannot show effect in people with Alzheimer's disease. Caterina Scuderi reports equipment, drugs or supplies provided by Epitech Group SpA, which makes ultramicronised PEA.

Source

PubMed 41496364 · doi:10.1016/j.biopha.2025.118965

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.