Protein Boost Resets Brain Rhythms and Memory in Alzheimer’s Mice

Gladstone Institutes researchers observed parvalbumin interneurons in awake mice and found that these cells fire in a precise sequence to generate gamma oscillations. In mice with Alzheimer’s-like disease, the sequence became disordered, with too many cells firing together and the gamma rhythm weakening. Increasing a specific protein restored the cells’ timing and improved memory in the animals, suggesting a possible therapeutic target.

Gamma rhythms are fast brain waves, cycling between 30 and 90 times per second, that support attention, learning, and recall. For decades, researchers have known these rhythms become weaker in Alzheimer’s disease, but the cellular choreography behind them was unclear.

In healthy awake mice, PV interneurons fired in ordered turns: early cells responded strongly, later groups were weaker, and about one-third stayed silent. Alzheimer’s-like mice showed disrupted timing, with sluggish early responders, overactive later cells, fewer quiet cells, and excessive synchrony. Boosting a specific protein restored timing and improved memory. Recordings also tied sudden drops in PV activity to epileptic spikes, which may relate to epilepsy-like activity in more than a quarter of Alzheimer’s patients.