{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:04:51Z","timestamp":1788822291191,"version":"build-2803163510"},"reference-count":45,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,10,13]]},"abstract":"<jats:p>Background: Alterations in the methionine cycle and abnormal tau phosphorylation are implicated in many neurodegenerative diseases, including Alzheimer\u2019s disease and frontotemporal dementia. rTg4510 mice express mutant human P301L tau and are a model of tau hyperphosphorylation. The cognitive deficit seen in these animals correlates with a burden of hyperphosphorylated tau and is a model to test therapies aimed at lowering phosphorylated tau. Objective: This study aimed to increase protein phosphatase 2A activity through supplementation of S-adenosylmethionine and analyze the effect on spatial memory and tau in treated animals. Methods: 6-month-old rTg4510 mice were treated with 100\u200amg\/kg S-adenosylmethionine by oral gavage for 3 weeks. Spatial recognition memory was tested in the Y-maze. Alterations to phosphorylated tau and protein phosphatase 2A were explored using immunohistochemistry, western blot, and enzyme-linked immunosorbent assays. Results: Treatment with S-adenosylmethionine increased the Y-maze novel arm exploration time and increased both the expression and activity of protein phosphatase 2A. Furthermore, treatment reduced the number of AT8 positive neurons and reduced the expression of phosphorylated tau (Ser202\/Thr205). S-adenosylmethionine contributes to multiple pathways in neuronal homeostasis and neurodegeneration. Conclusion: This study shows that supplementation with S-adenosylmethionine stabilizes the heterotrimeric form of PP2A resulting in an increase the enzymatic activity, a reduced level of pathological tau, and improved cognition.<\/jats:p>","DOI":"10.3233\/jad-200756","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T10:30:13Z","timestamp":1599561013000},"page":"1705-1715","source":"Crossref","is-referenced-by-count":18,"title":["S-Adenosylmethionine Rescues Cognitive Deficits in the rTg4510 Animal Model by Stabilizing Protein Phosphatase 2A and Reducing Phosphorylated Tau"],"prefix":"10.1177","volume":"77","author":[{"given":"Leah C.","family":"Beauchamp","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"},{"name":"Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang M.","family":"Liu","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Sedjahtera","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjana","family":"Bogeski","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Vella","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"},{"name":"Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley I.","family":"Bush","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"},{"name":"Melbourne Dementia Research Centre, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Adlard","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"},{"name":"Melbourne Dementia Research Centre, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Barnham","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia"},{"name":"Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Australia"},{"name":"Melbourne Dementia Research Centre, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-200756_ref1","doi-asserted-by":"crossref","first-page":"7501","DOI":"10.1073\/pnas.1504081112","article-title":"Tau stabilizes microtubules by binding at the interface between tubulin heterodimers","volume":"112","author":"Kadavath","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-200756_ref2","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1016\/S0021-9258(17)42989-9","article-title":"Phosphorylation affects the ability of tau protein to promote microtubule assembly","volume":"259","author":"Lindwall","year":"1984","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-200756_ref3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.21037\/atm.2018.04.23","article-title":"Tau in neurodegenerative disease","volume":"6","author":"Gao","year":"2018","journal-title":"Ann Transl Med"},{"key":"10.3233\/JAD-200756_ref4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/31508","article-title":"Association of missense and 5\u2019-splice-site mutations in tau with the inherited dementia FTDP-17","volume":"393","author":"Hutton","year":"1998","journal-title":"Nature"},{"key":"10.3233\/JAD-200756_ref5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0006-8993(92)91476-U","article-title":"Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments","volume":"597","author":"Ksiezak-Reding","year":"1992","journal-title":"Brain Res"},{"key":"10.3233\/JAD-200756_ref6","doi-asserted-by":"crossref","first-page":"24374","DOI":"10.1016\/S0021-9258(20)80536-5","article-title":"Microtubule-associated protein tau. 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