Cleaning Up the Spill: An Antibiotic’s Surprising Role in Alzheimer’s Defence

It appears an old drug may yet learn new tricks. Ceftriaxone, a stalwart antibiotic typically deployed against bacterial infections, has shown remarkable efficacy in restoring cognitive faculties in mice bred to mimic Alzheimer’s disease. The mechanism, revealed in a recent study, has little to do with bacteria and everything to do with cellular housekeeping.

In the chaotic environment of an Alzheimer’s-afflicted brain, a transporter protein known as GLT-1 often fails in its duties. Its primary role is to clear away glutamate, a neurotransmitter that excites neurons. When GLT-1 falters, glutamate spills out of the synaptic cleft—the communication gap between neurons—and accumulates in the 'extrasynaptic' wilderness. This spillover triggers specific receptors (eNMDARs) to fling open the cellular floodgates for calcium.

While calcium is vital for neuronal signalling, an uncontrolled deluge is catastrophic. The study reveals that this influx overwhelms the mitochondria, the cell’s power plants, causing them to lose structural integrity and fail. By administering ceftriaxone, researchers successfully upregulated GLT-1 levels, effectively mopping up the excess glutamate. This blockade prevented the calcium surge, preserved mitochondrial function, and, crucially, reversed memory deficits in the subjects. While human trials remain a distant prospect, the findings offer a compelling target for preserving the brain's energy supply.