{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:38:09Z","timestamp":1774507089474,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Individuals with <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic> (glucocerebrosidase) mutations are at increased risk of Parkinson's disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>). It is still debated, however, whether this increased risk results from impaired glucocerebrosidase activity leading to substrate accumulation. Comparing the presence of prodromal <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> marker in <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic> mutation carriers and patients with Gaucher disease (GD) (in which substrate accumulation is extensive) can assist in clarifying this issue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this cross\u2010sectional study, we compared the hyperechogenic area of the substantia nigra, a prodromal <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> marker, in large cohorts of <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic> mutation carriers (<jats:italic>n<\/jats:italic>\u00a0=\u00a071) and patients with GD (<jats:italic>n<\/jats:italic>\u00a0=\u00a0145). Our control populations were healthy, non\u2010carriers (<jats:italic>n<\/jats:italic>\u00a0=\u00a049) and patients with <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic>\u2010related <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a011). Substrate accumulation was assessed from dry blood spot levels of glucosylsphingosine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings indicate no contribution of substrate accumulation, as the area of hyperechogenicity is similarly enlarged relative to healthy controls in both <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic> mutation carriers and patients with GD. Moreover, this similarity between <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic> carriers and patients with GD persists when comparing only carriers of the N370S (c.1226A&gt;G) mutation (<jats:italic>n<\/jats:italic>\u00a0=\u00a038) with untreated patients with GD who were homozygotes for the same mutation (<jats:italic>n<\/jats:italic>\u00a0=\u00a047). In addition, measurements of hyperechogenic area did not correlate with levels of glucosylsphingosine in the untreated patients with GD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The presence of a marker of prodromal <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> (substantia nigra hyperechogenicity) is independent of substrate accumulation in a population with mutated <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic>. Although further longitudinal studies are needed to determine the precise predictive value of this marker for <jats:italic>\n<jats:styled-content style=\"fixed-case\">GBA<\/jats:styled-content>\n<\/jats:italic>\u2010related <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, our findings raise doubts regarding the contribution of substance reduction strategies to <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> prevention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13927","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T03:58:12Z","timestamp":1549252692000},"page":"1013-1018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for <i>GBA<\/i>\u2010related Parkinson's disease"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5065-991X","authenticated-orcid":false,"given":"D.","family":"Arkadir","sequence":"first","affiliation":[{"name":"Department of Neurology Hadassah Medical Center The Hebrew University  Jerusalem"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Dinur","sequence":"additional","affiliation":[{"name":"Gaucher Center Shaare Zedek Medical Center The Hebrew University  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Becker Cohen","sequence":"additional","affiliation":[{"name":"Gaucher Center Shaare Zedek Medical Center The Hebrew University  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Revel\u2010Vilk","sequence":"additional","affiliation":[{"name":"Gaucher Center Shaare Zedek Medical Center The Hebrew University  Jerusalem 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