{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:00:38Z","timestamp":1784797238336,"version":"3.55.0"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":203,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations in the glucocerebrosidase (GBA) gene, originally implicated in Gaucher\u2019s disease, are now recognized as a major risk factor for developing Parkinson\u2019s disease (PD). While up to 70% of PD patients eventually progress to dementia, GBA mutations further increase the risk of Lewy body dementias (LBD), an umbrella term encompassing both dementia with Lewy bodies and Parkinson\u2019s disease dementia. Collectively, these disorders are classified as synucleinopathies. To date, there is no clear understanding of the mechanistic relationships between GBA mutations and synucleinopathies, although, synaptic protein changes have been shown to correlate with cognitive change in LBD as well as in Alzheimer\u2019s disease (AD). The aim of this study was to examine synaptic dysfunction in \u03b1-synucleinopathies with GBA mutations. The research cohort consisted of 10 controls, 7 PD\/LBD-GBA N370S, and 20 PD\/LBD-wild type (WT) where seven synaptic markers including four pre-synaptic [synaptosomal-associated protein 25; (SNAP25), synaptophysin; (SYP), ras-related protein; (Rab3A), and vesicle associated membrane proteins 2; (VAMP2)], two post-synaptic [post-synaptic density protein 95; (PSD95), and neurogranin; (NRGN)], and one astrocytic [vesicle associated membrane proteins 3; (VAMP3)] protein were investigated in four cortical regions (prefrontal, temporal, anterior cingulate and parietal) using immunoblot technique. Four markers (NRGN, SNAP25, VAMP2, and VAMP3) were found to be significantly and regionally altered between the three groups. The expression of pre-synaptic (SNAP25), post-synaptic (NRGN), and the astrocytic protein (VAMP3) is different between PD\/LBD with GBA mutation and PD\/LBD-WT suggesting the potential role of GBA gene due to mutations which could alter the levels of some synaptic markers. Our study is the first to validate several synaptic markers in human post-mortem-associated GBA N370S mutation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag246","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T08:01:22Z","timestamp":1784793682000},"source":"Crossref","is-referenced-by-count":0,"title":["Altered synaptic and astrocytic proteins in Lewy body disorders associated with\n                    <i>GBA<\/i>\n                    mutations"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-8202","authenticated-orcid":false,"given":"Thamir M","family":"Eid","sequence":"first","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology , London WC1N 1PJ ,","place":["UK"]},{"name":"Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London SE5 8AB ,","place":["UK"]},{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University , Jeddah 21589 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7389-0348","authenticated-orcid":false,"given":"Tammaryn","family":"Lashley","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-6995","authenticated-orcid":false,"given":"Thomas T","family":"Warner","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology , London WC1N 1PJ ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Reta Lila Weston Institute, University College London Queen Square Institute of Neurology , London WC1N 1PJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9635-9027","authenticated-orcid":false,"given":"Alaa","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4697-5001","authenticated-orcid":false,"given":"Chanati","family":"Jantrachotechatchawan","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London SE5 8AB ,","place":["UK"]},{"name":"Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok 10700 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T","family":"Francis","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London SE5 8AB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3122-0423","authenticated-orcid":false,"given":"John","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Bandopadhyay","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London Queen 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