Longevity & AgingCaAKG Reverses Alzheimer's Synaptic Deficits in Mice via Autophagy Boost
Researchers at the National University of Singapore tested calcium alpha-ketoglutarate (CaAKG) — a TCA-cycle metabolite already linked to lifespan extension — in APP/PS1 Alzheimer's mice. CaAKG restored long-term potentiation (LTP) at hippocampal CA1 synapses, with stronger effects in females than males. The rescue worked through an NMDA-receptor-independent pathway involving L-type calcium channels and calcium-permeable AMPA receptors. CaAKG also elevated LC3-II, a marker of autophagy, and facilitated synaptic tagging and capture — a cellular model of associative memory. Rapamycin, an mTOR inhibitor, mirrored these effects in AD mice but paradoxically blocked LTP in wild-type animals, suggesting the autophagy pathway is particularly important when synaptic function is already compromised.
