Have you ever wondered if an ordinary molecule in our body’s metabolic cycle could be the secret weapon against the “eraser of memories” – Alzheimer’s disease? Recent scientific research has focused on a substance called alpha-ketoglutaric acid (AKG) and discovered its exciting brain-protective potential. What is AKG? Simply put, it is a key intermediate in the tricarboxylic acid cycle, the “energy factory” of our cells (mitochondria). It acts like a central gear in an engine, not only participating in energy production but also significantly influencing cell lifespan, inflammation, and gene expression. In recent years, scientists have found that supplementing with AKG can extend the healthy lifespan of various animals, making it a hot topic in anti-aging research. A new breakthrough: AKG “repairs” the brain networks in Alzheimer’s disease. A recent important study published in *Aging Cell* revealed that AKG and its more stable calcium salt form (CaAKG) play a crucial role in repairing the memory infrastructure in mice with Alzheimer’s disease models. Alzheimer’s disease is characterized not only by plaques and tangles in the brain but also by the premature and significant deterioration of synapses (the connections between neurons). You can think of synapses as the bridges of communication between friends, and long-term potentiation (LTP) is the process that makes these bridges stronger and signal transmission more efficient, which is the biological basis for forming and consolidating memories. In affected brains, these “bridges” become fragile and damaged. The study found that after administering AKG/CaAKG, LTP in the hippocampus (the memory center) of the diseased mice was significantly restored, indicating that the ability of synapses to communicate was reactivated. Notably, this reparative effect was more pronounced in female mice, providing new insights into the gender differences in the disease. How does AKG work? Its unique reparative mechanism bypasses the traditional NMDA receptor pathway, which is considered essential. Instead, it activates two other “backup channels” in the brain: L-type calcium channels, which act like specialized gates for calcium ions; and AMPA receptors, another type of receptor that allows calcium ions to enter. Through these pathways, CaAKG efficiently delivers the necessary calcium signals to damaged neurons, initiating the repair process. It also enhances the cell’s autophagy ability, the cell’s “cleaning” process, helping to remove metabolic waste accumulated in the brain and maintain a healthy neuronal environment. Even more surprisingly, AKG/CaAKG can repair cellular models of associative memory. For example, the ability to associate the smell of coffee with a certain morning scene is impaired in the early stages of Alzheimer’s disease. Research has shown that AKG/CaAKG helps to rebuild the cellular basis for this type of memory. From the lab to real life: Unlike many synthetic drugs, AKG is a naturally occurring substance in the human body, and its safety has been well-established. Studies have shown that its supplementation in humans is feasible and safe. This research provides the first systematic understanding of the role and unique mechanisms of AKG/CaAKG in combating synapse degeneration associated with Alzheimer’s disease. While the current findings are mainly based on animal models and brain slice studies, whether the same effects can be replicated in humans still requires further clinical trials. Nevertheless, this research opens a new door: by supplementing with natural metabolites like AKG, we may be on the path to a promising new nutritional intervention strategy for preventing and delaying Alzheimer’s disease and related age-related brain disorders, focusing on “improving brain cell communication” and “enhancing cellular self-cleaning.”