{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:31:57Z","timestamp":1773012717606,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017643","name":"Saastamoisen s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017643","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015736","name":"Folkh\u00e4lsanin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015736","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Progressive myoclonic epilepsy type 1 (EPM1) is a neurodegenerative disease caused by biallelic variants in the cystatin B (\n                      <jats:italic>CSTB<\/jats:italic>\n                      ) gene. Despite a progressive course, phenotype severity varies among patients, even within families. We studied the potential role of\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 in modifying phenotypic diversity in EPM1, given its established association with neurodegeneration, particularly in Alzheimer's disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE<\/jats:italic>\n                      genotypes were determined for 65 genetically verified EPM1 patients homozygous for the CSTB expansion mutation. The Unified Myoclonus Rating Scale (UMRS), Quality of Life in Epilepsy Inventory\u201031 questionnaire (QOLIE\u201031), intellectual ability (WAIS\u2010R), clinical data, and quantitative neuroimaging data were compared between\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers and noncarriers to assess potential correlations with EPM1 severity. Volumetric analysis was performed on MRI data, while diffusion tensor imaging (DTI) was analyzed using Tract\u2010Based Spatial Statistics (TBSS) and atlas\u2010based white matter (WM) tract region of interest (ROI) analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort included 20 \u03b54 carriers (16 \u03b53\/\u03b54 and 4 \u03b54\/\u03b54) and 45 \u03b54 noncarriers (36 \u03b53\/\u03b53, 8 \u03b52\/\u03b53, and 1 \u03b52\/\u03b52). No significant differences were found in UMRS or disease duration. Carriers had better QOLIE\u201031 scores in emotional well\u2010being (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.047), energy\/fatigue (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.048), and medical effects (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.024). In volumetric analysis, carriers exhibited greater preservation of bilateral hippocampal and amygdalar volumes but demonstrated more pronounced cortical thinning in the left lingual gyrus, right lateral occipital gyrus, and right posterior cingulate (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05). Carriers exhibited more widespread WM degeneration in DTI, characterized by reduced fractional anisotropy (FA) and increased mean diffusivity (MD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Despite greater white matter degeneration and reduced cortical thickness,\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers exhibited preserved deep brain volumes and better self\u2010reported well\u2010being. This study highlights the complex interplay between genetic factors and neurodegenerative processes. Our future research aims to provide more natural history data of EPM1 and correlate long\u2010term phenotypic data with additional geno\u2010phenotypic analyses.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70112","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:40:20Z","timestamp":1759506020000},"page":"55-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the role of apolipoprotein \u03b54 in progressive myoclonic epilepsy type 1"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-1653","authenticated-orcid":false,"given":"Janina","family":"Gunnar","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri","family":"Eronen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarja","family":"Joensuu","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Medicum, University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marja","family":"\u00c4iki\u00e4","sequence":"additional","affiliation":[{"name":"Kuopio Epilepsy Center, Kuopio University Hospital, Member of ERN EpiCARE  Kuopio 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