Mouse model uncovers early Alzheimer’s biomarker

Researchers at the University of Illinois Urbana-Champaign discovered that an early sign of Alzheimer’s disease is an increase in a specific protein in the brain. This protein, called PSD-95, is linked to seizures, one of the first signs of nerve damage.

By inhibiting this protein, the researchers could reduce the development and progression of seizures in mice. This finding implies that PSD-95 may provide a novel target for the diagnosis and therapy of Alzheimer’s disease.

Tsai said, “If we can catch anything happening early enough, maybe we can find a way to diagnose the disease earlier or slow down the progression. We know that Alzheimer’s is irreversible. But if we can slow down the progression or even delay the onset of the disease, we can improve the quality of life for patients.”

The researchers observed higher protein levels called PSD-95 during early neural development in both neuron cultures and live mice. PSD-95 facilitates the surface expression of receptors that enable neuronal communication. 

This increase in PSD-95 appears to make the brain more excitable, typical in the early stages of Alzheimer’s disease. By blocking PSD-95 in mice, the researchers reduced seizure activity and mortality, suggesting that PSD-95 plays a crucial role in causing seizures.

The researchers highlight the importance of PSD-95 in the early stages of Alzheimer’s, suggesting it could be an early warning sign for the disease or increased seizure risk. Our study published in EMBO Reports indicates that blocking PSD-95 with antibody inhibitors could be a potential treatment strategy. 

They also intend to study the relationship between PSD-95 and other synaptic surface receptors, like the NMDA receptor, which plays a role in Alzheimer’s disease-related cell death. The Alzheimer’s Association and the National Institutes of Health funded this research.

A new Alzheimer’s biomarker called PSD-95 was found in mice, suggesting new treatment options. PSD-95 could indicate early Alzheimer’s and seizure risk. Blocking PSD-95 in mice reduced seizures, showing promise for treatments. More research in humans is needed to fully understand PSD-95’s role in Alzheimer’s and its potential as a treatment target.

Journal reference:

1. Yeeun Yook, Kwan Young Lee, et al., Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology. EMBO reports. DOI: 10.1038/s44319-024-00090-0.