Researchers at the National University of Singapore have uncovered a natural aging-related molecule that could potentially restore memory functions impaired by Alzheimer’s disease. The study, published on January 25, 2026, highlights the role of calcium alpha-ketoglutarate (CaAKG) in improving communication between brain cells, thereby enhancing early memory abilities that are typically the first to fade in Alzheimer’s patients.
The research team, led by Professor Brian K Kennedy from the Yong Loo Lin School of Medicine, aimed to investigate whether CaAKG could mitigate the cognitive decline associated with aging and Alzheimer’s. The findings indicate that boosting this compound, which naturally declines with age, may provide a safer alternative for brain health maintenance.
Significant Breakthrough in Memory Restoration
This study marks a pivotal shift in understanding potential treatments for Alzheimer’s. The investigation examined whether CaAKG could enhance synaptic plasticity—an essential process for memory formation—restore memory-related signaling, and protect neurons from early degeneration. The results revealed that CaAKG not only improved brain cell communication but also repaired weakened neuronal signaling pathways disrupted by Alzheimer’s.
“Our findings reveal the exciting potential of longevity compounds in addressing Alzheimer’s disease,” stated Professor Kennedy. He emphasized that using natural compounds like CaAKG might complement existing treatments, making them safer and more accessible. As CaAKG is already present in the human body, targeting its pathways could minimize risks associated with new drug therapies.
Understanding the Mechanism Behind CaAKG
The research explored the impact of CaAKG on long-term potentiation (LTP), a critical process for learning and memory. In models of Alzheimer’s disease, LTP is severely impaired. Remarkably, CaAKG was found to restore this process to normal levels. Furthermore, the compound increased autophagy, the brain’s mechanism for removing damaged proteins, which is vital for maintaining neuronal health.
The study revealed that CaAKG operates through a newly identified pathway, enhancing neuronal flexibility by activating L-type calcium channels and calcium-permeable AMPA receptors. Notably, this approach avoids the NMDA receptors often compromised by amyloid plaque accumulation in Alzheimer’s.
Additionally, CaAKG restored synaptic tagging and capture, a mechanism essential for linking experiences and forming associative memories. This suggests that CaAKG could support not only basic memory functions but also higher-level cognitive abilities that are often diminished early in Alzheimer’s progression.
Dr. Sheeja Navakkode, the first author of the study and a research scientist at the Healthy Longevity Translational Research Programme, commented on the significance of their findings. “Understanding the cellular mechanisms of how CaAKG improves synaptic plasticity sheds light on new ways to protect memory and slow brain aging,” she said.
The implications of this research extend beyond Alzheimer’s treatment. By focusing on the biology of aging itself, scientists are paving the way for geroprotective strategies—treatments that could prevent age-related conditions before they manifest.
This innovative approach to enhancing brain health and potentially delaying cognitive decline opens new avenues for research and treatment, underscoring the importance of exploring natural compounds in the quest for solutions to age-related diseases.
