A Potential Blood-Based Marker for Alzheimer’s
Researchers from the University of Buenos Aires and CONICET have identified a drop in the brain protein mGlu3R as a potential early indicator of Alzheimer’s disease. Published in the Journal of Neurochemistry, the study reveals that levels of this protein—essential for neuroprotection and cognitive function—decline significantly in individuals suffering from mild cognitive impairment.
The Link Between GRM3 Activity and Brain Damage
The mGlu3R protein sits on the surface of brain cells, acting as a receptor for glutamate, the brain's primary excitatory neurotransmitter.
By analyzing human brain tissue and mouse models, researchers found that the GRM3 gene, which produces mGlu3R, loses activity in regions where beta-amyloid plaques accumulate. In animal models, these protein levels in astrocytes—the brain’s support cells—dropped before visible plaques even formed.
Measuring Protein Levels in Human Serum
The team successfully measured mGlu3R levels in human serum using standard laboratory techniques. In a pilot study of 20 volunteers, those with mild cognitive impairment showed significantly lower protein levels than participants with normal cognitive function.
"The diagnosis of Alzheimer’s disease, even in early stages, today includes biomarkers measurable in the plasma of patients, which reflect the deposit of the two proteins associated, such as beta-amyloid and tau," noted Gustavo Sevlever, director of research and teaching at Fleni and a co-author of the study.
Currently, diagnosis relies on costly brain imaging or cerebrospinal fluid analysis. This research points toward a less invasive alternative, as the team observed a positive correlation between mGlu3R and beta-amyloid levels in the blood.
The Need for Longitudinal Data
The researchers caution that these findings offer only a "snapshot" of protein levels and cannot yet predict individual risk. Because the study was limited to female participants, larger, longitudinal trials are required to validate the protein as a clinical tool.
"The idea would be to see the complete film, that is, to follow those people over time and determine the rate of Alzheimer’s development over the years," explained Gisela Novack, a postdoctoral fellow at CONICET and co-author of the study.
Future Paths for Clinical Intervention
The group is now preparing a follow-up trial with a larger, more diverse cohort to determine if this biomarker can effectively distinguish between various stages of cognitive decline. If successful, these findings could pivot the focus of future therapies toward protecting the mGlu3R receptor, providing a fresh avenue for intervention in patients showing early signs of impairment.