{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:20:05Z","timestamp":1785417605022,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,25]]},"group-title":"Neuroscience","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["AG077002"],"award-info":[{"award-number":["AG077002"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  4-Methylumbelliferone (4-MU) inhibits hyaluronic acid (HA) synthesis and is currently approved in Europe for biliary spasm. 4-MU administration reduces perineuronal nets (PNNs), and enzymatic degradation of PNNs in mouse models of Alzheimer\u2019s disease (AD) attenuates memory impairment. Although 4-MU has therapeutic efficacy in rodent models of fibrosis and cancer, it has not been examined in an Alzheimer\u2019s model. Here, we evaluated the impact of long-term 4-MU treatment in the APP\/PS1 amyloid mouse model. From three months of age, mice were on either a vehicle or 4-MU\u2013supplemented diet for 70 days or 52 weeks. Short and long-term 4-MU treatment decreased the soluble parenchymal A\u03b2\n                  <jats:sub>1-42<\/jats:sub>\n                  \/A\u03b2\n                  <jats:sub>1-40<\/jats:sub>\n                  ratio. Reductions in insoluble amyloid plaque were observed following 52 weeks of treatment. Extended 4-MU administration also reduced PNN intensity and ameliorated spatial memory deficits in APP\/PS1 mice. These findings provide support for targeting brain extracellular matrix (ECM) as a therapeutic strategy for AD.\n                <\/jats:p>","DOI":"10.64898\/2026.05.21.726929","type":"posted-content","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T16:15:17Z","timestamp":1779725717000},"source":"Crossref","is-referenced-by-count":0,"title":["4-methylumbelliferone attenuates amyloid pathology and learning deficits in the APP\/PS1 mouse model"],"prefix":"10.64898","author":[{"given":"Matthew","family":"Amontree","sequence":"first","affiliation":[{"name":"Georgetown University School of Medicine, Department of Neuroscience"},{"name":"Georgetown University School of Medicine, Interdisciplinary Program in Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Georgetown University School of Medicine, Department of 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