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Tau protein and beta-amyloid1-42 CSF levels in different phenotypes of Parkinson’s disease

  • Movement Disorders - Original Article
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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder with highly heterogeneous clinical manifestations. This fact has prompted many attempts to divide PD patients into clinical subgroups. This could lead to a better recognition of pathogenesis, improving targeted treatment and the prognosis of PD patients. The aim of the present study was to obtain cerebrospinal fluid (CSF) samples in PD patients and to search for a relationship between neurodegenerative CSF markers (tau protein, beta-amyloid1-42 and index tau protein/beta-amyloid1-42) and the clinical subtypes. PD patients were divided into three subgroups: early disease onset (EDO), tremor-dominant PD (TD-PD), and non-tremor dominant PD (NT-PD) according to the previously published classification. Neurodegenerative markers in the CSF were assessed in these three groups of patients suffering from PD (EDO-17, TD-15, NT-16 patients) and in a control group (CG) of 19 patients suffering from non-degenerative neurological diseases and 18 patients with Alzheimer’s disease (AD). The NT-PD patients were found to have significantly higher levels of CSF tau protein and index tau/beta than the control subjects and other Parkinsonian subgroups, but no significant differences in these markers were found between AD and NT-PD patients. In the context of more rapid clinical progression and more pronounced neuropathological changes in the NT-PD patient group, our results corroborate the opinion that CSF level of tau protein may be regarded as a potential laboratory marker of the presence and severity of neurodegeneration.

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References

  • Alves G, Brønnick K, Aarsland D, Blennow K, Zetterberg H, Ballard C et al (2010) CSF amyloid-{beta} and tau proteins, and cognitive performance, in early and untreated Parkinson’s Disease: the Norwegian ParkWest study. J Neurol Neurosurg Psychiatry 81:1080–1086

    Article  PubMed  Google Scholar 

  • Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, Ueda K et al (1999) Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in Lewy bodies in sporadic Parkinson’s disease and in dementia with Lewy bodies. Brain Res 843:53–61

    Article  PubMed  CAS  Google Scholar 

  • Bibl M, Mollenhauer B, Esselmann H, Lewczuk P, Klafki HW, Sparbier K et al (2006) CSF amyloid-beta-peptides in Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia. Brain 129:1177–1187

    Article  PubMed  Google Scholar 

  • Blennow K, Nellgĺrd B (2004) Amyloid beta 1-42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology 62(1):159–160

    Google Scholar 

  • Burn DJ, Rowan EN, Allan LM, Molloy S, O’Brien JT, McKeith IG (2006) Motor subtype and cognitive decline in Parkinson’s disease with dementia, and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 77:585–589

    Article  PubMed  CAS  Google Scholar 

  • Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D (2008) Dementia and survival in Parkinson’s disease. Neurology 70:1017–1022

    Article  PubMed  CAS  Google Scholar 

  • Clinton LK, Blurton-Jones M, Myczek K, Trojanowski JQ, LaFerla FM (2010) Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci 30:7281–7289

    Article  PubMed  CAS  Google Scholar 

  • Compta Y, Martí MJ, Ibarretxe-Bilbao N, Junqué C, Valldeoriola F, Muñoz E et al (2009) Cerebrospinal tau, phospho-tau, and beta-amyloid and neuropsychological functions in Parkinson’s disease. Mov Disord 24:2203–2210

    Article  PubMed  Google Scholar 

  • Esposito A, Dohm CP, Kermer P, Bähr M, Wouters FS (2007) Alpha-Synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiol Dis 26:521–531

    Article  PubMed  CAS  Google Scholar 

  • Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM et al (2007) Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64:343–349

    Article  PubMed  Google Scholar 

  • Goel V, Grafman J (1995) Are the frontal lobes implicated in `planning’ functions? Interpreting data from the Tower of Hanoi. Neuropsychologia 33:623–642

    Article  PubMed  CAS  Google Scholar 

  • Graham JM, Sagar HJ (1999) A data-driven approach to the study of heterogeneity in idiopathic Parkinson’s disease: identification of three distinct subtypes. Mov Disord 14:10–20

    Article  PubMed  CAS  Google Scholar 

  • Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442

    PubMed  CAS  Google Scholar 

  • Hu WT, Chen-Plotkin A, Arnold SE, Grossman M, Clark CM, Shaw LM et al (2010) Biomarker discovery for Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease. Acta Neuropathol 120(3):385–399

    Article  PubMed  Google Scholar 

  • 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 55:181–184

    Article  PubMed  CAS  Google Scholar 

  • Jellinger KA (2008) Neuropathological aspects of Alzheimer disease, Parkinson disease and frontotemporal dementia. Neurodegener Dis 5:118–121

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Jellinger KA, Seppi K, Wenning GK, Poewe W (2002) Impact of coexistent Alzheimer pathology on the natural history of Parkinson’s disease. J Neural Transm 109:329–339

    Article  PubMed  CAS  Google Scholar 

  • Lashley T, Holton JL, Gray E, Kirkham K, O’Sullivan SS, Hilbig A et al (2008) Cortical alpha-synuclein load is associated with amyloid-beta plaque burden in a subset of Parkinson’s disease patients. Acta Neuropathol 115:417–425

    Article  PubMed  CAS  Google Scholar 

  • Lee VM, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121–1159

    Article  PubMed  CAS  Google Scholar 

  • Lewis SJ, Foltynie T, Blackwell AD, Robbins TW, Owen AM, Barker RA (2005) Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 76:343–348

    Article  PubMed  CAS  Google Scholar 

  • Lyros E, Messinis L, Papathanasopoulos P (2008) Does motor subtype influence neurocognitive performance in Parkinson’s disease without dementia? Eur J Neurol 15:262–267

    Article  PubMed  CAS  Google Scholar 

  • Mattila PM, Koskela T, Röyttä M, Lehtimäki T, Pirttilä TA, Ilveskoski E et al (1998) Apolipoprotein E epsilon4 allele frequency is increased in Parkinson's disease only with co-existing Alzheimer pathology. Acta Neuropathol 96(4):417–420

    Google Scholar 

  • Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302(4):385–393

    Google Scholar 

  • Mollenhauer B, Trenkwalder C, von Ahsen N, Bibl M, Steinacker P, Brechlin P et al (2006) Beta-amyloid 1–42 and tau-protein in cerebrospinal fluid of patients with Parkinson’s disease dementia. Dement Geriatr Cogn Disord 22:200–208

    Article  PubMed  CAS  Google Scholar 

  • Obereigneru R, Obereigneru K, Cakirpaloglu S, Reiterova E, Kanovsky P (2010) Tower of Hanoi and the new administration rules for effective executive functions diagnostics. Eur J Neurol 17(Suppl 3):482

    Google Scholar 

  • Okonkwo OC, Alosco ML, Griffith HR, Mielke MM, Shaw LM, Trojanowski JQ et al (2010) Cerebrospinal fluid abnormalities and rate of decline in everyday function across the dementia spectrum: normal aging, mild cognitive impairment, and Alzheimer disease. Arch Neurol 67:688–696

    Article  PubMed  Google Scholar 

  • Ost M, Nylén K, Csajbok L, Ohrfelt AO, Tullberg M, Wikkelsö C et al (2006) Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology 67(9):1600–1604

    Google Scholar 

  • Pan S, Shi M, Jin J, Albin RL, Lieberman A, Gearing M et al (2007) Proteomics identification of proteins in human cortex using multidimensional separations and MALDI tandem mass spectrometer. Mol Cell Proteomics 6(10):1818–1823

    Google Scholar 

  • Paulus W, Jellinger K (1991) The neuropathological basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol 50:743–755

    Article  PubMed  CAS  Google Scholar 

  • Přikrylová Vranová H, Mareš J, Nevrlý M, Zapletalová J, Hluštík P, Kaňovský P (2010) CSF markers of neurodegeneration in Parkinson’s disease. J Neural Transm 117:1177–1181

  • Qureshi HY, Paudel HK (2011) Parkinsonian neurotoxin MPTP and alpha-synuclein mutations promote tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro. J Biol Chem 286(7):5055–5068

    Google Scholar 

  • Rajput A, Dickson DW, Robinson CA, Ross OA, Dächsel JC, Lincoln SJ et al (2006) Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology 67:1506–1508

    Article  PubMed  CAS  Google Scholar 

  • Rajput AH, Voll A, Rajput ML, Robinson CA, Rajput A (2009) Course in Parkinson disease subtypes: a 39-year clinicopathologic study. Neurology 73:206–212

    Article  PubMed  CAS  Google Scholar 

  • Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ (2004) Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 6(11):1054–1061

    Article  PubMed  CAS  Google Scholar 

  • Siderowf A, Xie SX, Hurtig H, Weintraub D, Duda J, Chen-Plotkin A et al (2010) CSF amyloid {beta}1-42 predicts cognitive decline in Parkinson disease. Neurology 75(12):1055–1061

    Article  PubMed  CAS  Google Scholar 

  • Spreen O, Strauss E (1998) A compendium of neuropsychological tests, 2nd edn. Oxford University Press, New York

    Google Scholar 

  • Stejskal D, Vavroušková J, Mareš J, Urbánek K (2005) Application of new laboratory marker assays in neurological diagnosis—a pilot study. Biomed Pap 149:265–267

    CAS  Google Scholar 

  • Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH et al (2003) Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 289(16):2094–2103

    Google Scholar 

  • van Rooden SM, Heiser WJ, Kok JN, Verbaan D, van Hilten JJ, Marinus J (2010) The identification of Parkinson’s disease subtypes using cluster analysis: a systematic review. Mov Disord 25(8):969–978

    Article  PubMed  Google Scholar 

  • van Rooden SM, Colas F, Martínez-Martín P, Visser M, Verbaan D, Marinus J et al (2011) Clinical subtypes of Parkinson’s disease. Mov Disord 26(1):51–58

    Article  PubMed  Google Scholar 

  • Waxman EA, Giasson BI (2011) Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tau. J Neurosci 31(21):7604–7618

    Article  PubMed  CAS  Google Scholar 

  • Williams DR, Lees AJ (2009) How do patients with parkinsonism present? A clinicopathological study. Intern Med J 39(1):7–12

    Article  PubMed  CAS  Google Scholar 

  • Yao C, Williams AJ, Ottens AK, May Lu XC, Chen R et al (2008) Detection of protein biomarkers using high-throughput immunoblotting following focal ischemic or penetrating ballistic-like brain injuries in rats. Brain Inj 22(10):723–732

    Google Scholar 

Download references

Acknowledgments

The study was supported by grant IGA MHCZ NT1222-5/2010.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic

    Hana Přikrylová Vranová, Jan Mareš, Petr Hluštík, Martin Nevrlý & Petr Kaňovský

  2. Department of Biochemistry, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Olomouc, Czech Republic

    David Stejskal

  3. Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Olomouc, Czech Republic

    Jana Zapletalová

  4. Department of Psychology, Philosophical Faculty, Palacky University in Olomouc, Olomouc, Czech Republic

    Radko Obereigneru

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  1. Hana Přikrylová Vranová
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  2. Jan Mareš
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Correspondence to Hana Přikrylová Vranová.

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Přikrylová Vranová, H., Mareš, J., Hluštík, P. et al. Tau protein and beta-amyloid1-42 CSF levels in different phenotypes of Parkinson’s disease. J Neural Transm 119, 353–362 (2012). https://doi.org/10.1007/s00702-011-0708-4

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  • DOI: https://doi.org/10.1007/s00702-011-0708-4

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