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Tramiprosate reduces misfolding of amyloid beta (A\u03b2) monomers and inhibits oligomer formation. In the present study, we investigated tramiprosate's effects on amyloidogenic processing of amyloid precursor protein (APP) and tau phosphorylation using the N2a\u2010APPSwe cell line as a cellular model of AD. Tramiprosate decreased levels of secreted A\u03b240 and A\u03b242 in a dose\u2010dependent manner without affecting cell viability. It also reduced the levels of APP, \u03b2\u2010site APP cleaving enzyme 1 (BACE1), and presenilin 1 C\u2010terminal fragment (PS1\u2010CTF) in this cellular model, indicating that tramiprosate may modulate amyloidogenic APP processing at multiple steps, thereby reducing A\u03b2 production. Additionally, tramiprosate decreased tau phosphorylation at Ser202\/Thr205 and Ser396\/Ser404 in a dose\u2010dependent manner while total tau level remained unchanged. Increased phosphorylation of glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2) at Ser9, without altering total GSK\u20103\u03b2 levels, suggests that GSK\u20103\u03b2 inhibition underlies the decrease in tau phosphorylation at these sites. As a result, tramiprosate's impact on both amyloidogenic APP processing and tau phosphorylation reveals its potential to modify AD.<\/jats:p>","DOI":"10.1002\/ddr.70330","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:04:54Z","timestamp":1780556694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tramiprosate, the Active Agent of ALZ\u2010801, Modulates Amyloidogenic APP Processing and Tau Phosphorylation in a Cellular Model of Alzheimer's Disease"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9285-0819","authenticated-orcid":false,"given":"Kevser","family":"Biberoglu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Pharmacy Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-5226","authenticated-orcid":false,"given":"Ozden","family":"Tacal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Pharmacy Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"219","article-title":"Clinical Benefits of Tramiprosate in Alzheimer's Disease Are Associated With Higher Number of APOE4 Alleles: The \u201cAPOE4 Gene\u2010Dose Effect","volume":"3","author":"Abushakra S.","year":"2016","journal-title":"Journal of Prevention of Alzheimer's Disease"},{"key":"e_1_2_9_3_1","first-page":"149","article-title":"Clinical Effects of Tramiprosate in APOE4\/4 Homozygous Patients With Mild Alzheimer's Disease Suggest Disease Modification Potential","volume":"4","author":"Abushakra S.","year":"2017","journal-title":"=Journal of Prevention of Alzheimer's Disease"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","unstructured":"Abushakra S. A.Power D.Watson et al.2025. Clinical Efficacy Safety and Imaging Effects of Oral Valiltramiprosate in APOE\u03b54\/\u03b54 Homozygotes With Early Alzheimer's Disease: Results of the Phase III Randomized Double\u2010Blind Placebo\u2010Controlled 78\u2010Week APOLLOE4 Trial: S. Abushakra et al. 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