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We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early tau pathology and synaptic degeneration in Alzheimer\u2019s 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 Alzheimer\u2019s disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.<\/jats:p>","DOI":"10.1101\/2024.05.12.593733","type":"posted-content","created":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T15:00:11Z","timestamp":1715526011000},"source":"Crossref","is-referenced-by-count":0,"title":["PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6754-6003","authenticated-orcid":false,"given":"Alexandre","family":"Poirier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Picard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Labont\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Aubry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Auld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the PREVENT-AD research group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel L.","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judes","family":"Poirier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024051511250431000_2024.05.12.593733v1.1","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Serra R , Alonso-Nanclares L , Cho K , Giese KP . Emerging insights into synapse dysregulation in Alzheimer\u2019s disease. Brain Communications. 2022;4(2).","DOI":"10.1093\/braincomms\/fcac083"},{"key":"2024051511250431000_2024.05.12.593733v1.2","doi-asserted-by":"crossref","unstructured":"Cornejo F , Cort\u00e9s BI , Findlay GM , Cancino GI . LAR Receptor Tyrosine Phosphatase Family in Healthy and Diseased Brain. 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