nach oben

Erschienen in:

20.08.2016 | Original Communication

Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies

verfasst von: Franc Llorens, Matthias Schmitz, Daniela Varges, Niels Kruse, Nadine Gotzmann, Karin Gmitterová, Brit Mollenhauer, Inga Zerr

Erschienen in: Journal of Neurology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

Several studies have addressed the utility of cerebrospinal (CSF) α-synuclein levels as a potential biomarker of α-synuclein aggregation disorders. However, its relevance in the differential diagnostic context of neurodegenerative and movement disorders is still a contentious subject. Here, we report total CSF α-synuclein levels in a cohort of clinically diagnosed α-synuclein-related disorders encompassing Parkinson’s disease, Parkinson’s disease dementia, dementia with Lewy bodies and multiple system atrophy in comparison to essential tremor and neurological control cases. α-synuclein levels in α-synuclein-related disorders were significantly lower than in controls (p < 0.001). However, in the differential diagnostic context, only Parkinson’s disease cases presented significant lower α-synuclein levels compared to essential tremor and neurological controls. In cases with clinically diagnosed α-synuclein pathology, CSF α-synuclein levels showed a moderate positive correlation with CSF tau and p-tau, but not with Aβ42 levels. Due to elevated CSF tau levels in dementia with Lewy bodies samples, tau/α-synuclein ratio showed a good clinical accuracy in discriminating controls from dementia with Lewy bodies cases (AUC = 0.8776) compared to single α-synuclein (AUC = 0.7192) and tau (AUC = 0.7739) levels. In conclusion, α-synuclein alone lacks of clinical value as a biomarker of α-synuclein-related disorders, but in combination with total tau, it may improve the diagnosis of dementia with Lewy bodies.

Boutin E, Vaugoyeau M, Eusebio A, Azulay JP, Witjas T (2015) News and controversies regarding essential tremor. Rev Neurol (Paris) 171(5):415–425CrossRef

Cummings JL (1988) Intellectual impairment in Parkinson’s disease: clinical, pathologic, and biochemical correlates. J Geriatr Psychiatry Neurol 1(1):24–36PubMedCrossRef

Eller M, Williams DR (2011) alpha-Synuclein in Parkinson disease and other neurodegenerative disorders. Clin Chem Lab Med 49(3):403–408PubMedCrossRef

Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22(12):1689–1707PubMedCrossRef

Ferrer I, Lopez-Gonzalez I, Carmona M, Dalfo E, Pujol A, Martinez A (2012) Neurochemistry and the non-motor aspects of PD. Neurobiol Dis 46(3):508–526PubMedCrossRef

Galvin JE, Lee VM, Trojanowski JQ (2001) Synucleinopathies: clinical and pathological implications. Arch Neurol 58(2):186–190PubMedCrossRef

Gao L, Tang H, Nie K, Wang L, Zhao J, Gan R, Huang J, Zhu R, Feng S, Duan Z, Zhang Y, Wang L (2015) Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson’s disease diagnosis: a systematic review and meta-analysis. Int J Neurosci 125(9):645–654PubMedCrossRef

Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71(9):670–676PubMedPubMedCentralCrossRef

Hall S, Ohrfelt A, Constantinescu R, Andreasson U, Surova Y, Bostrom F, Nilsson C, Hakan W, Decraemer H, Nagga K, Minthon L, Londos E, Vanmechelen E, Holmberg B, Zetterberg H, Blennow K, Hansson O (2012) Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol 69(11):1445–1452PubMedCrossRef

10.

Hall S, Surova Y, Ohrfelt A, Zetterberg H, Lindqvist D, Hansson O (2015) CSF biomarkers and clinical progression of Parkinson disease. Neurology 84(1):57–63PubMedPubMedCentralCrossRef

11.

Halliday GM, Leverenz JB, Schneider JS, Adler CH (2014) The neurobiological basis of cognitive impairment in Parkinson’s disease. Mov Disord 29(5):634–650PubMedPubMedCentralCrossRef

12.

Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184PubMedPubMedCentralCrossRef

13.

Jellinger KA (2009) A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders. Biochim Biophys Acta 1792(7):730–740PubMedCrossRef

14.

Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, Agundez JA (2012) The relationship between Parkinson’s disease and essential tremor: review of clinical, epidemiologic, genetic, neuroimaging and neuropathological data, and data on the presence of cardinal signs of parkinsonism in essential tremor. Tremor Other Hyperkinet Mov (N Y) 2:1–10

15.

Kaerst L, Kuhlmann A, Wedekind D, Stoeck K, Lange P, Zerr I (2014) Using cerebrospinal fluid marker profiles in clinical diagnosis of dementia with Lewy bodies, Parkinson’s disease, and Alzheimer’s disease. J Alzheimers Dis 38(1):63–73PubMed

16.

Kasai T, Tokuda T, Ishii R, Ishigami N, Tsuboi Y, Nakagawa M, Mizuno T, El-Agnaf OM (2014) Increased alpha-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. J Neurol 261(6):1203–1209PubMedCrossRef

17.

Kruse N, Schulz-Schaeffer WJ, Schlossmacher MG, Mollenhauer B (2012) Development of electrochemiluminescence-based singleplex and multiplex assays for the quantification of alpha-synuclein and other proteins in cerebrospinal fluid. Methods 56(4):514–518PubMedCrossRef

18.

Li X, Li TQ, Andreasen N, Wiberg MK, Westman E, Wahlund LO (2014) The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer’s disease. J Intern Med 275(4):418–427PubMedCrossRef

19.

Lim X, Yeo JM, Green A, Pal S (2013) The diagnostic utility of cerebrospinal fluid alpha-synuclein analysis in dementia with Lewy bodies—a systematic review and meta-analysis. Parkinsonism Relat Disord 19(10):851–858PubMedCrossRef

20.

Llorens F, Kruse N, Schmitz M, Shafiq M, da Cunha JE, Gotzman N, Zafar S, Thune K, de Oliveira JR, Mollenhauer B, Zerr I (2015) Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD. J Neurol 262(10):2305–2311PubMedCrossRef

21.

Llorens F, Schmitz M, Gloeckner SF, Kaerst L, Hermann P, Schmidt C, Varges D, Zerr I (2015) Increased albumin CSF/serum ratio in dementia with Lewy bodies. J Neurol Sci 358(1–2):398–403PubMedCrossRef

22.

Llorens F, Schmitz M, Karch A, Cramm M, Lange P, Gherib K, Varges D, Schmidt C, Zerr I, Stoeck K (2016) Comparative analysis of cerebrospinal fluid biomarkers in the differential diagnosis of neurodegenerative dementia. Alzheimers Dement 12(5):577–589PubMedCrossRef

23.

Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB (2005) Essential tremor associated with focal nonnigral Lewy bodies: a clinicopathologic study. Arch Neurol 62(6):1004–1007PubMedCrossRef

24.

McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 9(3 Suppl):417–423PubMed

25.

McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47(5):1113–1124PubMedCrossRef

26.

Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I, Ng J, Schulz-Schaeffer W, Kretzschmar HA, McLean PJ, Trenkwalder C, Sarracino DA, Vonsattel JP, Locascio JJ, El-Agnaf OM, Schlossmacher MG (2008) Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 213(2):315–325PubMedCrossRef

27.

Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Doring F, Trenkwalder C, Schlossmacher MG (2011) alpha-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10(3):230–240PubMedCrossRef

28.

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(3):332–335PubMedCrossRef

29.

Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S (2002) Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58(2):192–197PubMedCrossRef

30.

Pahwa R, Koller WC (1993) Is there a relationship between Parkinson’s disease and essential tremor? Clin Neuropharmacol 16(1):30–35PubMedCrossRef

31.

Parnetti L, Chiasserini D, Bellomo G, Giannandrea D, De CC, 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/alpha-synuclein ratio in Parkinson’s disease and degenerative dementias. Mov Disord 26(8):1428–1435PubMedCrossRef

32.

Sako W, Murakami N, Izumi Y, Kaji R (2014) Reduced alpha-synuclein in cerebrospinal fluid in synucleinopathies: evidence from a meta-analysis. Mov Disord 29(13):1599–1605PubMedCrossRef

33.

Schade S, Mollenhauer B (2014) Biomarkers in biological fluids for dementia with Lewy bodies. Alzheimers Res Ther 6(5–8):72PubMedPubMedCentralCrossRef

34.

Schoonenboom NS, Reesink FE, Verwey NA, Kester MI, Teunissen CE, van de Ven PM, Pijnenburg YA, Blankenstein MA, Rozemuller AJ, Scheltens P, van der Flier WM (2012) Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 78(1):47–54PubMedCrossRef

35.

Spies PE, Melis RJ, Sjogren MJ, Rikkert MG, Verbeek MM (2009) Cerebrospinal fluid alpha-synuclein does not discriminate between dementia disorders. J Alzheimers Dis 16(2):363–369PubMed

36.

Spillantini MG, Goedert M (2000) The alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Ann N Y Acad Sci 920:16–27PubMedCrossRef

37.

Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, Pirttila T (2009) Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66(3):382–389PubMedCrossRef

38.

Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J (2013) CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer’s disease. Acta Neuropathol 126(5):683–697PubMedCrossRef

39.

van Harten AC, Kester MI, Visser PJ, Blankenstein MA, Pijnenburg YA, van der Flier WM, Scheltens P (2011) Tau and p-tau as CSF biomarkers in dementia: a meta-analysis. Clin Chem Lab Med 49(3):353–366PubMed

40.

Vann Jones SA, O’Brien JT (2014) The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med 44(4):673–683PubMedCrossRef

41.

Walker Z, Possin KL, Boeve BF, Aarsland D (2015) Lewy body dementias. Lancet 386(10004):1683–1697PubMedCrossRef

42.

Wang ZY, Han ZM, Liu QF, Tang W, Ye K, Yao YY (2015) Use of CSF alpha-synuclein in the differential diagnosis between Alzheimer’s disease and other neurodegenerative disorders. Int Psychogeriatr 27(9):1429–1438PubMedCrossRef

43.

Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35PubMedCrossRef

44.

Zaccai J, McCracken C, Brayne C (2005) A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 34(6):561–566PubMedCrossRef

45.

Zhou B, Wen M, Yu WF, Zhang CL, Jiao L (2015) The diagnostic and differential diagnosis utility of cerebrospinal fluid alpha-synuclein levels in Parkinson’s disease: a meta-analysis. Parkinsons Dis 2015:567386PubMedPubMedCentral

Titel: Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies
verfasst von: Franc Llorens
Matthias Schmitz
Daniela Varges
Niels Kruse
Nadine Gotzmann
Karin Gmitterová
Brit Mollenhauer
Inga Zerr
Publikationsdatum: 20.08.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 11/2016
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-016-8259-0

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2016

Gender-based analysis of cortical thickness and structural connectivity in Parkinson’s disease

Vestibular function in patients with Niemann-Pick type C disease

An early case of a natural barrier to axonal degeneration

Efficacy and safety of short-term dual- versus mono-antiplatelet therapy in patients with ischemic stroke or TIA: a meta-analysis of 10 randomized controlled trials

A novel mutation m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism

Efficacy of single versus three sessions of high rate repetitive transcranial magnetic stimulation in chronic migraine and tension-type headache

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie