{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:38Z","timestamp":1792785818081,"version":"4.5.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Zealand Parkinson\u2019s Progression Programme"},{"DOI":"10.13039\/501100001505","name":"New Zealand Health Research Council","doi-asserted-by":"publisher","award":["14\/440"],"award-info":[{"award-number":["14\/440"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009477","name":"Lottery Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009477","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014191","name":"Brain Research New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Besides motor symptoms, many individuals with Parkinson\u2019s disease develop cognitive impairment perhaps due to coexisting \u03b1-synuclein and Alzheimer\u2019s disease pathologies and impaired brain insulin signalling. Discovering biomarkers for cognitive impairment in Parkinson\u2019s disease could help clarify the underlying pathogenic processes and improve Parkinson\u2019s disease diagnosis and prognosis.<\/jats:p>\n                  <jats:p>This study used plasma samples from 273 participants: 103 Parkinson\u2019s disease individuals with normal cognition, 121 Parkinson\u2019s disease individuals with cognitive impairment (81 with mild cognitive impairment, 40 with dementia) and 49 age- and sex-matched controls. Plasma extracellular vesicles enriched for neuronal origin were immunocaptured by targeting the L1 cell adhesion molecule, then biomarkers were quantified using immunoassays.<\/jats:p>\n                  <jats:p>\u03b1-Synuclein was lower in Parkinson\u2019s disease compared to control individuals (P = 0.004) and in cognitively impaired Parkinson\u2019s disease individuals compared to Parkinson\u2019s disease with normal cognition (P &amp;lt; 0.001) and control (P &amp;lt; 0.001) individuals. Amyloid-\u03b242 did not differ between groups. Phosphorylated tau (T181) was higher in Parkinson\u2019s disease than control individuals (P = 0.003) and in cognitively impaired compared to cognitively normal Parkinson\u2019s disease individuals (P &amp;lt; 0.001) and controls (P &amp;lt; 0.001). Total tau was not different between groups. Tyrosine-phosphorylated insulin receptor substrate-1 was lower in Parkinson\u2019s disease compared to control individuals (P = 0.03) and in cognitively impaired compared to cognitively normal Parkinson\u2019s disease individuals (P = 0.02) and controls (P = 0.01), and also decreased with increasing motor symptom severity (P = 0.005); serine312-phosphorylated insulin receptor substrate-1 was not different between groups. Mechanistic target of rapamycin was not different between groups, whereas phosphorylated mechanistic target of rapamycin trended lower in cognitively impaired compared to cognitively normal Parkinson\u2019s disease individuals (P = 0.05). The ratio of \u03b1-synuclein to phosphorylated tau181 was lower in Parkinson\u2019s disease compared to controls (P = 0.001), in cognitively impaired compared to cognitively normal Parkinson\u2019s disease individuals (P &amp;lt; 0.001) and decreased with increasing motor symptom severity (P &amp;lt; 0.001). The ratio of insulin receptor substrate-1 phosphorylated serine312 to insulin receptor substrate-1 phosphorylated tyrosine was higher in Parkinson\u2019s disease compared to control individuals (P = 0.01), in cognitively impaired compared to cognitively normal Parkinson\u2019s disease individuals (P = 0.02) and increased with increasing motor symptom severity (P = 0.003). \u03b1-Synuclein, phosphorylated tau181 and insulin receptor substrate-1 phosphorylated tyrosine contributed in diagnostic classification between groups.<\/jats:p>\n                  <jats:p>These findings suggest that both \u03b1-synuclein and tau pathologies and impaired insulin signalling underlie Parkinson\u2019s disease with cognitive impairment. Plasma neuronal extracellular vesicles biomarkers may inform cognitive prognosis in Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awac258","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T09:42:17Z","timestamp":1657791737000},"page":"195-208","source":"Crossref","is-referenced-by-count":93,"title":["Extracellular vesicle biomarkers for cognitive impairment in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5551-9219","authenticated-orcid":false,"given":"Joseph","family":"Blommer","sequence":"first","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Pitcher","sequence":"additional","affiliation":[{"name":"New Zealand Brain Research Institute , Christchurch 8011 , New Zealand"},{"name":"Department of Medicine, University of Otago , Christchurch 8011 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Mustapic","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erden","family":"Eren","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J","family":"Yao","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Vreones","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna A","family":"Pucha","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dalrymple-Alford","sequence":"additional","affiliation":[{"name":"New Zealand Brain Research Institute , Christchurch 8011 , New Zealand"},{"name":"School of Psychology, Speech and Hearing, University of Canterbury , Christchurch 8041 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Shoorangiz","sequence":"additional","affiliation":[{"name":"New Zealand Brain Research Institute , Christchurch 8011 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassilios G","family":"Meissner","sequence":"additional","affiliation":[{"name":"New Zealand Brain Research Institute , Christchurch 8011 , New Zealand"},{"name":"University of Bordeaux, CNRS, IMN, UMR 5293 , F-33000 Bordeaux , France"},{"name":"Service de Neurologie\u2014Maladies Neurod\u00e9g\u00e9n\u00e9ratives, CHU Bordeaux , F-33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Anderson","sequence":"additional","affiliation":[{"name":"New Zealand Brain Research Institute , Christchurch 8011 , New Zealand"},{"name":"Department of Medicine, University of Otago , Christchurch 8011 , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2181-3118","authenticated-orcid":false,"given":"Dimitrios","family":"Kapogiannis","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation , Baltimore, MD 21224 , 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