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Moreover, in a recent study, we identified the first family with autosomal dominant late\u2010onset Alzheimer's disease (AD) caused by a heterozygous\n                      <jats:italic>NPC1<\/jats:italic>\n                      mutation. Unfortunately, there are currently no effective treatments available for this condition. Miglustat, which impacts the metabolism of oxysterols, has been shown to exert an anti\u2010amyloidogenic effect in a human cellular model of AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In our exploratory uncontrolled study, three patients from the previously published family were orally treated with miglustat for 12\u2009months. They underwent monthly clinical evaluations and routine blood tests. Additionally, neuropsychological evaluations, brain amyloid\u2010PET imaging, and biochemical analyses on plasma and CSF were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All three patients achieved clinical stability, showed a sustained reduction in serum oxysterol levels, and experienced a marked decrease in brain amyloid burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Based on our preliminary observations and hypothesis\u2010generating findings, along with the growing evidence suggesting AD as a lipid disorder, miglustat should be further tested in a larger cohort of heterozygous\n                      <jats:italic>NPC1<\/jats:italic>\n                      mutated patients and probably evaluated as a potential disease\u2010modifying treatment for AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70419","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:43:36Z","timestamp":1762857816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Miglustat in Alzheimer's Disease Associated With Heterozygous\n                    <scp>\n                      <i>NPC1<\/i>\n                    <\/scp>\n                    Mutation: Exploratory Case Series and Preliminary Findings"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2256-0482","authenticated-orcid":false,"given":"Diego","family":"Lopergolo","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences University of Siena  Siena Italy"},{"name":"UOC Neurologia Azienda Ospedaliero\u2010Universitaria Senese  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4893-2146","authenticated-orcid":false,"given":"Daniele","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences University of Siena  Siena Italy"},{"name":"UOC Neurologia Azienda Ospedaliero\u2010Universitaria Senese  Siena Italy"},{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9950-0571","authenticated-orcid":false,"given":"Silvia","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences University of Siena  Siena Italy"},{"name":"UOC Neurologia Azienda Ospedaliero\u2010Universitaria Senese  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-6151","authenticated-orcid":false,"given":"Barbara","family":"Pucci","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9977-0706","authenticated-orcid":false,"given":"Domenico","family":"Tripodi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pathology and Toxicology, Hospital Pio XI of Desio, ASST Brianza, School of Medicine and Surgery University\u00a0of Milano Bicocca  Milan Italy"},{"name":"Department of Science and Technology (DST) University of Sannio  Benevento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-0366","authenticated-orcid":false,"given":"Valerio","family":"Leoni","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4094-9942","authenticated-orcid":false,"given":"Andrea","family":"Chincarini","sequence":"additional","affiliation":[{"name":"National Institute of Nuclear Physics (INFN)  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4886-2756","authenticated-orcid":false,"given":"Stelvio","family":"Sestini","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Unit of Nuclear Medicine PO\u2010S. 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