{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:01:29Z","timestamp":1778864489164,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["21 1426 Pj 01 H"],"award-info":[{"award-number":["21 1426 Pj 01 H"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["24 3500 Pj 01 H"],"award-info":[{"award-number":["24 3500 Pj 01 H"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In Alzheimer's disease (AD) there is accumulation of amyloid\u2010\u03b2 (A\u03b2) and hyperphosphorylated tau (pTau) in the brain. A\u03b2 activates kinases that phosphorylate tau. Increased pTau181 is a signal for hyperphosphorylation of tau. The generation of A\u03b2 from amyloid precursor protein (APP) and the release of heparan sulfate (HS) from the proteoglycan glypican\u20101 (GPC1) are interconnected. Release of HS is APP\u2010, ascorbate\u2010, copper\u2010, and NO\u2010dependent. HS\u2010A\u03b2 interactions may regulate tau phosphorylation in human neural stem cells (NSC). The most influential risk factor for sporadic AD is the presence of the \u03b54 allele of apolipoprotein E (ApoE). Here, we have further explored the interplay between GPC1\u2010derived HS and pTau181 formation in human neural progenitor cells (NPC) and induced neurons (iN) obtained by reprogramming of human fibroblasts from ApoE3\u2010 and ApoE4\u2010carriers. HS release from GPC1 was either suppressed or stimulated, and effects on pTau181 were monitored by immunofluorescence microscopy and quantified by intensity measurements as well as by enzyme\u2010linked immunosorbent assay (ELISA) technique. Stimulation of HS release decreased pTau181 in NSC but was without effect in NPC, where tau was mostly in the nuclei. However, suppression of HS release in NPC increased pTau181. Stimulation of HS release decreased pTau181 in ApoE4\/4\u2010iN but not in ApoE3\/3\u2010iN. A high intake of vitamin C may be of prophylactic value in ApoE4\u2010positive individuals.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70162-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70162","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T11:45:08Z","timestamp":1752752708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of\n                    <scp>pTau181<\/scp>\n                    by Glypican\u20101\u2010Derived Heparan Sulfate in Human Neural Progenitor Cells and\n                    <scp>ApoE4<\/scp>\n                    \u2010Expressing Induced Neurons"],"prefix":"10.1111","volume":"169","author":[{"given":"Fang","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Experimental Medical Science, Division of Neuroscience, Glycobiology Group Lund University  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars\u2010\u00c5ke","family":"Fransson","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Division of Neuroscience, Glycobiology Group Lund University  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-0634","authenticated-orcid":false,"given":"Katrin","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Division of Neuroscience, Glycobiology Group Lund University  Lund 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