Your browser doesn't support javascript.
loading
Extracellular vesicle biomarkers for cognitive impairment in Parkinson's disease.
Blommer, Joseph; Pitcher, Toni; Mustapic, Maja; Eren, Erden; Yao, Pamela J; Vreones, Michael P; Pucha, Krishna A; Dalrymple-Alford, John; Shoorangiz, Reza; Meissner, Wassilios G; Anderson, Tim; Kapogiannis, Dimitrios.
Afiliação
  • Blommer J; National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
  • Pitcher T; New Zealand Brain Research Institute, Christchurch 8011, New Zealand.
  • Mustapic M; Department of Medicine, University of Otago, Christchurch 8011, New Zealand.
  • Eren E; National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
  • Yao PJ; National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
  • Vreones MP; National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
  • Pucha KA; National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
  • Dalrymple-Alford J; National Institute on Aging, Intramural Research Program, Laboratory of Clinical Investigation, Baltimore, MD 21224, USA.
  • Shoorangiz R; New Zealand Brain Research Institute, Christchurch 8011, New Zealand.
  • Meissner WG; School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8041, New Zealand.
  • Anderson T; New Zealand Brain Research Institute, Christchurch 8011, New Zealand.
  • Kapogiannis D; New Zealand Brain Research Institute, Christchurch 8011, New Zealand.
Brain ; 146(1): 195-208, 2023 01 05.
Article em En | MEDLINE | ID: mdl-35833836
ABSTRACT
Besides motor symptoms, many individuals with Parkinson's disease develop cognitive impairment perhaps due to coexisting α-synuclein and Alzheimer's disease pathologies and impaired brain insulin signalling. Discovering biomarkers for cognitive impairment in Parkinson's disease could help clarify the underlying pathogenic processes and improve Parkinson's disease diagnosis and prognosis. This study used plasma samples from 273

participants:

103 Parkinson's disease individuals with normal cognition, 121 Parkinson's 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. α-Synuclein was lower in Parkinson's disease compared to control individuals (P = 0.004) and in cognitively impaired Parkinson's disease individuals compared to Parkinson's disease with normal cognition (P < 0.001) and control (P < 0.001) individuals. Amyloid-ß42 did not differ between groups. Phosphorylated tau (T181) was higher in Parkinson's disease than control individuals (P = 0.003) and in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P < 0.001) and controls (P < 0.001). Total tau was not different between groups. Tyrosine-phosphorylated insulin receptor substrate-1 was lower in Parkinson's disease compared to control individuals (P = 0.03) and in cognitively impaired compared to cognitively normal Parkinson's 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's disease individuals (P = 0.05). The ratio of α-synuclein to phosphorylated tau181 was lower in Parkinson's disease compared to controls (P = 0.001), in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P < 0.001) and decreased with increasing motor symptom severity (P < 0.001). The ratio of insulin receptor substrate-1 phosphorylated serine312 to insulin receptor substrate-1 phosphorylated tyrosine was higher in Parkinson's disease compared to control individuals (P = 0.01), in cognitively impaired compared to cognitively normal Parkinson's disease individuals (P = 0.02) and increased with increasing motor symptom severity (P = 0.003). α-Synuclein, phosphorylated tau181 and insulin receptor substrate-1 phosphorylated tyrosine contributed in diagnostic classification between groups. These findings suggest that both α-synuclein and tau pathologies and impaired insulin signalling underlie Parkinson's disease with cognitive impairment. Plasma neuronal extracellular vesicles biomarkers may inform cognitive prognosis in Parkinson's disease.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Doença de Alzheimer / Insulinas / Disfunção Cognitiva Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Doença de Alzheimer / Insulinas / Disfunção Cognitiva Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article