Researchers at the National University of Singapore have discovered that calcium alpha-ketoglutarate, a naturally occurring molecule, can repair key memory processes disrupted by Alzheimer's disease. The compound improves communication between brain cells and restores early memory abilities that fade first in the condition. Since it already exists in the body and declines with age, boosting it could offer a safer approach to protecting brain health.
Scientists at the Yong Loo Lin School of Medicine, National University of Singapore, are exploring ways to alter the biology of aging to prevent conditions like Alzheimer's disease. In a study published in Aging Cell, a team led by Professor Brian K. Kennedy, chair of the Healthy Longevity Translational Research Programme, examined calcium alpha-ketoglutarate (CaAKG), a metabolite linked to healthy aging.
The research focused on Alzheimer's models and found that CaAKG restores synaptic plasticity, a process essential for learning and memory. It repaired weakened signaling between neurons and revived associative memory, one of the first cognitive functions affected by the disease. The molecule also boosted long-term potentiation (LTP), which strengthens neural connections, and enhanced autophagy, the brain's mechanism for clearing damaged proteins.
CaAKG works by activating L-type calcium channels and calcium-permeable AMPA receptors, while bypassing NMDA receptors often impaired by amyloid buildup. This action also restored synaptic tagging and capture, aiding the brain in linking experiences to form memories.
"Our findings reveal the exciting potential of longevity compounds in addressing Alzheimer's disease," Prof. Kennedy said. "The research suggests that safe, natural compounds like CaAKG may one day complement existing approaches to protect the brain and slow memory loss. Because AKG is already present in our bodies, targeting these pathways may offer fewer risks and broader accessibility."
Dr. Sheeja Navakkode, the study's first author and a research scientist at the programme, added: "Our goal was to determine whether a compound originally explored for extending healthy lifespan could be helpful for Alzheimer's disease. Understanding the cellular mechanisms of how CaAKG improves synaptic plasticity sheds light on new ways to protect memory and slow brain aging."
These results suggest a shift toward geroprotective strategies that target aging itself, potentially delaying cognitive decline before severe damage occurs. The study was conducted on APP/PS1 mice models of Alzheimer's disease.
