Correlates of cerebrospinal fluid levels of oligomeric- and total-α-synuclein in premotor, motor and dementia stages of Parkinson’s disease

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• 作者：Yaroslau Compta ; Tony Valente ; Josep Saura ; Bàrbara Segura…
• 关键词：Parkinson’s disease ; Premotor ; Dementia ; Cerebrospinal fluid ; α ; Synuclein ; Cortical thickness ; Neuropsychological function
• 刊名：Journal of Neurology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：262
• 期：2
• 页码：294-306
• 全文大小：1,214 KB
• 参考文献：1. Mollenhauer B (2014) Quantification of α-synuclein in cerebrospinal fluid: how ideal is this biomarker for Parkinson’s disease? Parkinsonism Relat Disord 20(Suppl 1):S76–S79 CrossRef
  2. Magdalinou N, Lees AJ, Zetterberg H (2014) Cerebrospinal fluid biomarkers in parkinsonian conditions: an update and future directions. J Neurol Neurosurg Psychiatry 85:1065-075 CrossRef
  3. Tolosa E, Gaig C, Santamaría J, Compta Y (2009) Diagnosis and the premotor phase of Parkinson disease. Neurology 72:S12–S20 CrossRef
  4. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197-11 CrossRef
  5. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord 23:837-44 CrossRef
  6. Braak H, Rüb U, Jansen Steur EN, Del Tredici K, de Vos RA (2005) Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 64:1404-410 CrossRef
  7. Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J (2010) DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133:713-26 CrossRef
  8. Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T, Ishigami N, Tamaoka A, Nakagawa M, El-Agnaf OM (2010) Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75:1766-772 CrossRef
  9. Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-D?ring F, Trenkwalder C, Schlossmacher MG (2011) α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10:230-40 CrossRef
  10. Parnetti L, Chiasserini D, Bellomo G, Giannandrea D, De Carlo C, Qureshi MM, Ardah MT, Varghese S, Bonanni L, Borroni B, Tambasco N, Eusebi P, Rossi A, Onofrj M, Padovani A, Calabresi P, El-Agnaf O (2011) Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson’s disease and degenerative dementias. Mov Disord 26:1428-435 CrossRef
  11. Kang JH, Irwin DJ, Chen-Plotkin AS, Parkinson’s Progression Markers Initiative et al (2013) Association of cerebrospinal fluid β-amyloid 1-42, T-tau, P-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol 70:1277-287
  12. van Dijk KD, Bidinosti M, Weiss A, Raijmakers P, Berendse HW, van de Berg WD (2014) Reduced α-synuclein levels in cerebrospinal fluid in Parkinson’s disease are unrelated to clinical and imaging measures of disease severity. Eur J Neurol 21:388-94 CrossRef
  13. Ohrfelt A, Grognet P, Andreasen N, Wallin A, Vanmechelen E, Blennow K, Zetterberg H (2009) Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci Lett 450:332-35 CrossRef
  14. Park MJ, Cheon SM, Bae HR, Kim SH, Kim JW (2011) Elevated levels of α-synuclein oligomer in the cerebrospinal fluid of drug-na?ve patients with Parkinson’s disease. J Clin Neurol 7:215-22 CrossRef
  15. Aerts MB, Esselink RA, Abdo WF, Bloem BR, Verbeek MM (2012) CSF α-synuclein does not differentiate between parkinsonian disorders. Neurobiol Aging 33:43
• 作者单位：Yaroslau Compta (1)
  Tony Valente (2)
  Josep Saura (2)
  Bàrbara Segura (3)
  álex Iranzo (4)
  Mònica Serradell (4)
  Carme Junqué (3)
  Eduard Tolosa (1)
  Francesc Valldeoriola (1)
  Esteban Mu?oz (1)
  Joan Santamaria (4)
  Ana Cámara (1)
  Manel Fernández (1)
  Juan Fortea (5)
  Mariateresa Buongiorno (1)
  José Luis Molinuevo (5)
  Núria Bargalló (6)
  María José Martí (1)
  
  1. Parkinson’s Disease and Movement Disorders Unit, Neurology Service, ICN, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, 170 Villarroel, 08036, Barcelona, Catalonia, Spain
  2. Biochemistry and Molecular Biology Unit, School of Medicine, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain
  3. Department of Psychiatry and Clinical Psychobiology, IDIBAPS, CIBERNED, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain
  4. Multidisciplinary Sleep Disorders Unit and Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, Barcelona, Catalonia, Spain
  5. Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Catalonia, Spain
  6. Neuroradiology Section, Magnetic Resonance Unit, Centre de Diagnòstic per la Imatge (CDI), Hospital Clínic and Imaging Research Platform, IDIBAPS, Barcelona, Catalonia, Spain
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Neurology
  Neurosciences
  Neuroradiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1459

文摘

High-oligomeric and low-total-α-synuclein cerebrospinal fluid (CSF) levels have been found in Parkinson’s disease (PD), but with inconsistent or limited data, particularly on their clinical and structural correlates in earliest (premotor) or latest (dementia) PD stages. We determined CSF oligomeric- and total-α-synuclein in 77 subjects: 23 with idiopathic REM-sleep behaviour disorder (iRBD, a condition likely to include a remarkable proportion of subjects in the premotor stage of PD) and 41 with PD [21 non-demented (PDND)?+?20 demented (PDD)], intended to reflect the premotor–motor–dementia PD continuum, along with 13 healthy controls. The study protocol also included the Unified PD Rating Scale motor-section (UPDRS-III), mini mental state examination (MMSE), neuropsychological cognitive testing, 3T brain MRI for cortical-thickness analyses, CSF τ and CSF Aβ. CSF oligomeric-α-synuclein was higher in PDND than iRBD and in PDD than iRBD and controls, and correlated with UPDRS-III, MMSE, semantic fluency and visuo-perceptive scores across the proposed premotor–motor–dementia PD continuum (iRBD?+?PDND?+?PDD). CSF total-α-synuclein positively correlated with age, CSF Aβ, and, particularly, CSF τ, tending towards lower levels in PD (but not iRBD) vs. controls only when controlling for CSF τ. Low CSF total-α-synuclein was associated with dysfunction in phonetic-fluency (a frontal-lobe function) in PD and with frontal cortical thinning in iRBD and PDND independently of CSF τ. Conversely, the associations of high (instead of low)?CSF total-α-synuclein with posterior-cortical neuropsychological deficits in PD and with posterior cortical thinning in PDD were driven by high CSF τ. These findings suggest that CSF oligomeric- and total-α-synuclein have different clinical, neuropsychological and MRI correlates across the proposed premotor–motor–dementia PD continuum. CSF total-α-synuclein correlations with CSF τ and Aβ support the hypothesis of an interaction among these proteins in PD, with CSF τ probably influencing the presence of high (instead of low)?CSF total-α-synuclein and its correlates mostly in the setting of PD-related dementia.