Pan-AMPK activator MK-8722 improves spatial memory in Alzheimer's model mice
Systemic treatment activated liver AMPK, restored plasma metabolites, and enhanced dendritic spine maturation without altering hippocampal long-term potentiation.
Journal of neurochemistry · Nicol NI et al. · Paper published 1 Oct 2026
In APP/PS1 Alzheimer's disease model mice aged six to eight months, researchers tested whether systemic administration of the pan-AMPK activator MK-8722 altered cognitive function, synaptic plasticity, and circulating metabolic profiles. The compound was well tolerated and activated AMPK in the liver, but it did not activate AMPK in the hippocampus. Despite this peripheral localization, MK-8722 selectively improved hippocampal-dependent spatial memory deficits and enhanced hippocampal dendritic spine maturation. However, treatment did not change hippocampal long-term potentiation. Profiling of plasma lipidomics and metabolomics revealed coordinated disruptions in glycerophosphatidylcholine species, glutathione cycling, carnitine-dependent fatty acid transport, and the kynurenine pathway in the diseased mice. Systemic MK-8722 treatment partially normalized these circulating metabolic networks.
Why it matters
The findings show that activating metabolic regulators outside the brain can remodel systemic metabolism and improve aspects of cognitive and synaptic health in neurodegenerative disease.
Caveats
The study was conducted exclusively in a mouse model, and the intervention failed to alter hippocampal long-term potentiation or directly activate AMPK in brain tissue.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
AMPK Activator MK-8722 Improves Spatial Memory Deficit and Alters Metabolome in APP/PS1 AD Mouse Model
Nicol NI, Li T, Su Q et al.
Journal of neurochemistry · 1 Oct 2026 · Peer-reviewed
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