PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer's disease

Poirier, A.; Picard, C.; Labonte, A.; Aubry, I.; Auld, D.; Zetterberg, H.; Blennow, K.; the PREVENT-AD research group,; Tremblay, M.; Poirier, J.

doi:10.1101/2024.05.12.593733

bioRxiv · 10.1101/2024.05.12.593733

PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer's disease

Poirier, A.·Picard, C.·Labonte, A.·Aubry, I.·Auld, D.·Zetterberg, H.·Blennow, K.·the PREVENT-AD research group,·Tremblay, M.·Poirier, J.

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Abstract

We examined the role of protein tyrosine phosphatase receptor sigma (PTPRS) in the context of Alzheimers 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 Alzheimers disease biomarkers. We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early tau pathology and synaptic degeneration in Alzheimers disease. This single nucleotide polymorphism correlated with higher PTPRS transcript abundance and lower P-tau181 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 Alzheimers disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.

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Poirier, A., Picard, C., Labonte, A., Aubry, I., Auld, D., Zetterberg, H., Blennow, K., the PREVENT-AD research group,, Tremblay, M., Poirier, J.. 2024-05-12. PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer's disease. https://doi.org/10.1101/2024.05.12.593733

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