{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:23:04Z","timestamp":1790266984440,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T00:00:00Z","timestamp":1611964800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Medical Faculty at Lund University"},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gunvor och Josef An\u00e9rs Foundation and the Dementia Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Apolipoprotein E4 (ApoE4) genotype is the most influential risk factor for sporadic Alzheimer\u2019s disease. It appears to be associated with retarded endosome-to-autophagosome trafficking. The amyloid precursor protein (APP) and the heparan sulfate (HS)-containing proteoglycan glypican-1 (Gpc-1) are both processed in endosomes, and mutually regulated by the APP degradation products and the released HS. We have investigated APP and Gpc-1 processing in ApoE3 and ApoE4 expressing human fibroblasts, in human neural stem cells (NSC) exposed to the cholesterol transport inhibitor U18666A and in induced neurons obtained by reprogramming of ApoE fibroblasts (ApoE-iN). We have used immunofluorescence microscopy, flow cytometry, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis western blotting with antibodies recognizing the released HS, APP, amyloid \u03b2(A\u03b2), late endosomes (Rab7), autophagosomes (LC3) and neurons (Tuj1). We found that the capacity to release HS was not fully utilized in ApoE4 expressing fibroblasts and that HS-A\u03b2 complexes accumulated in the nuclei. In ApoE3 fibroblasts, the \u03b2-cleaved APP C-terminal fragment (\u03b2-CTF) and A\u03b2 were primarily present in late endosomes and autophagosomes. When HS release from Gpc-1 was enhanced by ascorbate in ApoE4\/4 fibroblasts, there was efficient transfer of A\u03b2 and HS from the nuclei to autophagosomes. In U18666A-treated NSC as well as in ApoE4\/4-iN we repeatedly found accumulation of APP degradation products (\u03b2-CTF\/A\u03b2). This was reversed by subsequent exposure to ascorbate or dehydroascorbic acid.<\/jats:p>","DOI":"10.1093\/glycob\/cwaa120","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T07:23:14Z","timestamp":1609140194000},"source":"Crossref","is-referenced-by-count":4,"title":["Reversal of apolipoprotein E4-dependent or chemical-induced accumulation of APP degradation products by vitamin C-induced release of heparan sulfate from glypican-1"],"prefix":"10.1093","author":[{"given":"Fang","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Experimental Medical Science, Division of Neuroscience, Glycobiology Group, Lund University, Biomedical Center A13, SE-221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-\u00c5ke","family":"Fransson","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Division of Neuroscience, Glycobiology Group, Lund University, Biomedical Center A13, SE-221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Biomedical Center A13, SE-221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,30]]},"reference":[{"key":"2021020805442513700_ref1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic A\u03b2 oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat Neurosci"},{"key":"2021020805442513700_ref2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nrm2820","article-title":"Sensors and regulators of intracellular 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