Natural metabolite may restore memory in Alzheimer’s disease

The study found that CaAKG improves brain cell communication in models of Alzheimer’s disease. Not only does it restore weakened signals between neurons, but it also helps restore associative memory, one of the first functions to suffer in this disease. Because AKG levels in the body decline with age, replenishing it may be a promising way to support brain health and reduce the risk of neurodegenerative disorders.

To understand how CaAKG works, scientists studied long-term potentiation (LTP), a process by which connections between neurons are strengthened. The LTP plays a key role in learning and long-term memory formation, but is severely impaired in Alzheimer’s disease. Researchers have found that CaAKG is able to restore this process to normal levels.

In addition, CaAKG enhances autophagy, the brain’s natural cleansing system that removes damaged proteins and maintains healthy nerve cells. It acts through a recently described signaling pathway to make neurons more adaptive: activating L-type calcium channels and calcium-permeable AMPA receptors, while avoiding NMDA receptors, which are often damaged due to amyloid accumulation.

Importantly, CaAKG also restores the process of synaptic marking and capture, a mechanism that allows the brain to associate events with each other and form associative memories. This indicates that the drug may support not only basic memory functions, but also more complex learning skills that begin to decline in the early stages of Alzheimer’s disease.