PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer’s disease (Poirier A. et al., 2024)

Citation :
Poirier A, Picard C, Labonté A, and the Alzheimer Disease Neuroimaging Intiative, Zetterberg H, Blennow K, Tremblay M and Poirier J, for the PREVENT-AD research group (2024). PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer’s disease. Scientific Reports .

Full text : Here

Poirier A., Picard C., Labonté A., Auld D., and Alzheimer Disease Neuroimaging Initiative, Zetterberg H., Blennow K., Tremblay M., and Poirier J., for the PREVENT-AD research group

published in Nature Scientific Reports, June 2024.

ABSTRACT: We examined the role of protein tyrosine phosphatase receptor sigma (PTPRS) in the context of Alzheimer’s disease and synaptic integrity. Publicly available datasets (BRAINEAC, ROSMAP, ADC1) and a cohort of asymptomatic but “at risk” individuals (PREVENT-AD) were used to explore the relationship between PTPRS and various Alzheimer’s disease biomarkers. We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early Tau pathology and synaptic degeneration in Alzheimer’s disease. This single nucleotide polymorphism correlated with higher PTPRS transcript abundance and lower p(181)Tau and GAP-43 levels in the CSF. In the brain, PTPRS protein abundance was significantly correlated with the quantity of two markers of synaptic integrity: SNAP25 and SYT-1. We also found the presence of sexual dimorphism for PTPRS, with higher CSF concentrations in males than females. Male carriers for variant C were found to have a 10-month delay in the onset of AD. We thus conclude that PTPRS acts as a neuroprotective receptor in Alzheimer’s disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.