Clinical value of CSF amyloid-beta-42 and tau proteins in Progressive Supranuclear Palsy

  • Tommaso Schirinzi
  • Giulia Maria Sancesario
  • Giulia Di Lazzaro
  • Simona Scalise
  • Vito Luigi Colona
  • Paola Imbriani
  • Nicola Biagio Mercuri
  • Sergio Bernardini
  • Anthony E. Lang
  • Antonio Pisani
Neurology and Preclinical Neurological Studies - Original Article

Abstract

Progressive Supranuclear Palsy (PSP) is a four-repeat tauopathy with high phenotypic and neuropathological variability, highlighting the urgent need for effective disease biomarkers. Quantitative analysis of cerebrospinal fluid (CSF) proteins reflecting pathological changes of CNS is currently used as biomarkers of multiple neurodegenerative disorders for both early differential diagnosis and prognostic clustering of patients. In this study, we thus assessed the clinical usefulness of a panel of CSF biomarker in PSP patients presenting with Richardson’s Syndrome. CSF levels of 42-beta-amyloid, total-tau, phosphorylated-tau, and both 42-beta-amyloid/phosphorylated-tau and phosphorylated-tau/total-tau ratios were comparatively evaluated in 39 PSP patients, 31 patients with Parkinson’s Disease (PD) and 58 gender-/age-matched healthy controls. Specific gold-standard clinical scores were obtained. Diagnostic accuracy and clinical correlates of each biomarker were measured with receiver operating curve analysis and Spearman’s test/linear regression, respectively. In PSP, 42-beta-amyloid was lower than either controls or PD; total-tau and phosphorylated-tau were instead reduced compared to controls, but similar to PD. At the cut-off value of 623 pg/ml, 42-beta-amyloid significantly distinguished PSP from controls and PD. Likewise, phosphorylated-tau/total-tau ratio also supported differential diagnosis between PSP and PD (cut-off = 0.185). 42-beta-amyloid was inversely associated with PSP severity, as measured with PSP Rating Scale. Our study demonstrates that CSF 42-beta-amyloid is reduced in PSP patients, proportionally to clinical severity, thus suggesting a potential use as disease biomarker. Moreover, phosphorylated-tau/total-tau ratio resulted helpful in the early differential diagnosis between PSP and PD.

Keywords

Progressive Supranuclear Palsy CSF biomarkers Parkinson’s Disease Amyloid-beta 

Notes

Funding

The study has been partially supported by the Italian Ministry of Healthy GR-2011-0234982.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.

Ethical approval

All procedures were conducted in agreement with indications of “good clinical practice”, and either to institutional/local ethical standards or ethical principles of Helsinki Declaration.

Informed consent

Informed consent was obtained from each participant included in the study.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Tommaso Schirinzi
    • 1
  • Giulia Maria Sancesario
    • 2
    • 3
  • Giulia Di Lazzaro
    • 1
  • Simona Scalise
    • 1
  • Vito Luigi Colona
    • 1
  • Paola Imbriani
    • 1
    • 2
  • Nicola Biagio Mercuri
    • 1
    • 2
  • Sergio Bernardini
    • 3
  • Anthony E. Lang
    • 4
  • Antonio Pisani
    • 1
    • 2
  1. 1.Department of Systems MedicineUniversity of Roma Tor VergataRomeItaly
  2. 2.IRCCS Fondazione Santa LuciaRomeItaly
  3. 3.Department of Experimental Medicine and SurgeryUniversity of Roma Tor VergataRomeItaly
  4. 4.Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders ClinicToronto Western HospitalTorontoCanada

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