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NEUROCHEMISTRY & BIOMARKERS UNIT

Neurochemistry Unit, 1st Department of Neurology,

National and Kapodistrian University of Athens,

Athens, Greece.

 

Heads of Neurochemistry and Biomarkers Unit:

  • Foteini Boufidou, Associate Professor of Medical Microbiology (Head of Neurochemistry and Biomarkers Unit Laboratory)
  • Vasilios Constantinides, Assistant Professor of Neurology (Clinical Head of Neurochemistry and Biomarkers Unit)

Senior Investigators:

Elisabeth Kapaki, Professor Emeritus of Neurology-Neurochemistry

George Paraskevas, Professor of Neurology-Neuropsychology

Educational activity

The Unit provides educational activities mainly at postgraduate level by welcoming and guiding postgraduate diploma students, PhD candidates and research fellows with a special interest in the field.

Contact

Information & appointments:

10:00a.m. - 14:00 p.m. (Monday to Friday)

Τel.: +30 210 7289125, e-mail: aneurochem[at]gmail[dot]com

 

Laboratory/research activity

Neurochemistry and Biomarker Unit is an independent unit of the 1st Department of Neurology since 1995. Between 1995 and 2023, Professor Elisabeth Kapaki, former Head of the Unit in collaboration with Professor George Paraskevas established a variety of neurochemical methods for the study of neurodegenerative disorders. Atomic Absorption Spectrophotometry and High-pressure Liquid Chromatography methodologies have been used for the detection of trace elements, free amino acids, monoamines, substances related to oxidative stress, such as ascorbic acid, vitamin E and glutathione in CSF and serum samples.

During the past two decades, the main focus of the Unit has been the implementation of cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers. These included the quantification of total tau (T-tau), phosphorylated tau (P-tau), beta-amyloid peptide with 42 (Aβ42) and with 40 (Aβ40) in the CSF. Results of this activity have been published in high impact factor journals and have been included in the European guidelines for the diagnosis and treatment of dementia (EFNS Task Force 2007) as well as in the Greek guidelines of the Hellenic’s Neurological Society Dementia Branch. The Unit has participated in various international quality control programs such as “The Alzheimer’s Association Quality Control program for CSF biomarkers” conducted by the University of Goethenburg and sponsored by the Alzheimer’s Association. It has also been a partner in the Joint Program on Neurodegenerative Diseases (JPND) - Biological markers for Alzheimer's disease and Parkinson's Disease (BIOMARKAPD) (2012). This activity has led to significant contribution regarding pre-analytical and analytical recommendations for CSF sample handling towards harmonization of standard operation procedures worldwide and reduction of intra-laboratory variation.

Moreover, in a collaboration with the Laboratory for Neurodegenerative Disorders of the Biomedical Research Foundation Academy of Athens and the Hamad Bin Khalifa University the Unit was involved in a promising effort to introduce CSF α-synuclein levels as a surrogate biomarker for synucleinopathies (Parkinson’s disease, Dementia with Lewy bodies, Multiple System Atrophy).

Currently, a collaboration with NKUA’s Medical School Laboratory for Biological Chemistry that involves CSF and plasma matrix metaloproteinases activity as well as inflammatory biomarkers in vascular cognitive disorders is in progress. Accordingly, CSF TDP-43 and plasma progranulin levels are under evaluation as potential surrogate biomarkers for the FTD-ALS spectrum. Their correlation with classical biomarkers in different genetic subtypes of FTD-ALS aims for highlighting novel personalized therapies.

Biobank

Since 1995, the Unit is maintaining a significant CSF and blood Biobank from over 1500 neurologic patients and over 20 different diagnoses, including rare ones. All samples, kept in -80⁰C, have been collected and handled according to strict international guidelines.

Clinical activity

Since 2022, the Unit provides medical services by receiving CSF samples and measuring specific AD biomarkers and the full biochemical CSF profile for AD (T-tau, P-Tau, Aβ42 and Aβ42/40 ratio).

This service is addressed to neurologists and their patients through a research account of NKUA (ELKE) as well as to public neurological clinics through Eginition Hospital. CSF samples are analyzed on EUROIMMUN Analyzer I (EUROIMMUN, Lübeck), a system for fully automated ELISA processing, combined with EUROIMMUN ELISA kits for optimal accuracy which is longitudinally evaluated through participation in “The Alzheimer’s Association QC program for CSF biomarkers”.

The Unit is the only one in Greece having its own control group of carefully selected, after a thorough neuropsychological evaluation, cognitively healthy individuals.

In recognition of its achievements, the Unit has been proposed by the National Observatory on Dementia and Alzheimer's Disease as well as the Hellenic Neurological Society to become Reference Laboratory for the measurement of Alzheimer’s disease biomarkers in CSF.

Relevant brochures in Greek:

 

PUBLICATIONS

BOOKS IN GREEK

  1. Σύγχρονη θεραπευτική θεώρηση της νόσου Alzheimer και άλλων ανοικών διαταραχών. E.Kapaki, G.Paraskevas. BHTA medical arts, Athens, 2004
  2. Συστάσεις για την διάγνωση της νόσου Alzheimer και άλλων διαταραχών σχετιζόμενων με άνοια: Κατευθυντήριες οδηγίες της Ευρωπαϊκής Ομοσπονδίας Νευρολογικών Εταιρειών.  Hellenic Neurological Society Dementia Branch. Editors:  Kapaki E, Beredimas P, Kosta V, Paraskevas GP. Psichogios publications, Athens, 2007
  3. Ρέοντας στο Κεντρικό Νευρικό Σύστημα: Οδηγός για το Εγκεφαλονωτιαίο Υγρό. F.Boufidou, E.Kapaki. Broken Hill Publishers LTD, Nicosia, Cyprus, 2022

 

Selective publications in scientific journals

 

  1. Kapaki E, Paraskevas GP, Michalopoulou M, Kilidireas K. Increased cerebrospinal fluid tau protein in multiple sclerosis. Eur Neurol. 2000;43(4):228-32.
  2. Kapaki E, Kilidireas K, Paraskevas GP, Michalopoulou M, Patsouris E. Highly increased CSF tau protein and decreased beta-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease? J Neurol Neurosurg Psychiatry. 2001;71(3):401-3.
  3. Wollmer A, Papasssotiropoulos A, Streffer J, Grimaldi L, Kapaki E, Paraskevas G, Maddalena A, De Quervain D, Bieber C, Umbricht D, Lemke U, Bossardt S, Degonda N, Henke-Westerholt K, Hegi T, Jung H, Pasch T, Hess K, Hock C, Nitsch R. Genetic polymorphisms and CSF levels of TIMP-1 in sporadic Alzheimer’s disease.  Psychiatric Genetics 2002; 12: 155-160.                    
  4. Kapaki E, Paraskevas G.P, Zalonis J, Zournas C. CSF tau protein and b-Amyloid (1–42) in Alzheimer’s disease diagnosis: Discrimination from normal ageing and other dementias in the Greek population. European Journal of Neurology 2003; 10: 119-128.
  5. Finckh U, Kuschel C, Anagnostouli M, Patsouris E, Pantes G, Gatzonis S, Kapaki E, Davaki P, Lamszus K, Stavrou D, Gal A. Novel mutations and repeated findings of mutations in familial Alzheimer disease. Neurogenetics 2005; 6: 85-89.
  6. Paraskevas G, Kapaki E,  Liappas I, Theotoka I,  Mamali I, Zournas C, Lykouras L. The diagnostic value of cerebrospinal fluid tau protein in dementing and non-dementing neuropsychiatric disorders.Journal of  Geriatric Psychiatry and Neurology 2005; 18: 163-173.           
  7. Kapaki EN, Paraskevas GP, Tzerakis NG, Sfagos C, Seretis A, Kararizou E, et al. Cerebrospinal fluid tau, phospho-tau181 and beta-amyloid1-42 in idiopathic normal pressure hydrocephalus: a discrimination from Alzheimer's disease. Eur J Neurol. 2007;14(2):168-73.
  8. Kapaki E, Paraskevas GP, Papageorgiou SG, Bonakis A, Kalfakis N, Zalonis I, et al. Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord. 2008;22(1):47-53.
  9. Paraskevas GP, Kasselimis D, Kourtidou E, Constantinides V, Bougea A, Potagas C, et al. Cerebrospinal Fluid Biomarkers as a Diagnostic Tool of the Underlying Pathology of Primary Progressive Aphasia. J Alzheimers Dis. 2017;55(4):1453-61.
  10. Constantinides VC, Paraskevas GP, Emmanouilidou E, Petropoulou O, Bougea A, Vekrellis K, et al. CSF biomarkers beta-amyloid, tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes. J Neurol Sci. 2017; 382:91-5.
  11. Paraskevas GP, Bougea A, Constantinides VC, Bourbouli M, Petropoulou O, Kapaki E. In vivo Prevalence of Alzheimer Biomarkers in Dementia with Lewy Bodies. Dement Geriatr Cogn Disord. 2019;47(4-6):289-96.
  12. Kapaki E, Constantinides VC, Pyrgelis E-S, Paraskevas PG, Papatriantafyllou JD, Paraskevas GP. Biomarker-based diagnosis of cognitive disorders in a case series. Neuroimmunology and Neuroinflammation. 2020;7(3):319-29.
  13. Constantinides VC, Paraskevas GP, Boufidou F, Bourbouli M, Stefanis L, Kapaki E. Cerebrospinal fluid biomarker profiling in corticobasal degeneration: Application of the AT(N) and other classification systems. Parkinsonism Relat Disord. 2021; 82:44-9.
  14. Constantinides VC, Majbour NK, Paraskevas GP, Abdi I, Safieh-Garabedian B, Stefanis L, et al. Cerebrospinal Fluid alpha-Synuclein Species in Cognitive and Movements Disorders. Brain sciences. 2021;11(1).
  15. Paraskevas GP, Constantinides VC, Boufidou F, Tsantzali I, Pyrgelis ES, Liakakis G, et al. Recognizing Atypical Presentations of Alzheimer’s Disease: The Importance of CSF Biomarkers in Clinical Practice. Diagnostics. 2022;12(12).
  16. Kapaki E, Boufidou F, Bourbouli M, Pyrgelis ES, Constantinides VC, Anastassopoulou C, et al. Cerebrospinal Fluid Biomarker Profile in TDP-43-Related Genetic Frontotemporal Dementia. J Pers Med. 2022;12(10).
  17. Kapaki E, Boufidou F, Bourbouli M, Pyrgelis ES, Constantinides VC, Anastassopoulou C, Paraskevas GP. Cerebrospinal Fluid Biomarker Profile in TDP-43-Related Genetic Frontotemporal Dementia. J Pers Med. 2022 Oct 21;12(10):1747.
  18. Kapaki E, Vakrakou AG, Boufidou F. Novel CSF Biomarkers Tracking Autoimmune Inflammatory and Neurodegenerative Aspects of CNS Diseases. Diagnostics (Basel). 2022 Dec 27;13(1):73
  19. Kapaki E., Boufidou F. Eds. Special Issue of the Journal “Diagnostics”: Advances in Cerebrospinal Fluid Diagnostics. 2022 (www.mdpi.com/journal/diagnostics/special_issues/CSF_Diagnosis)
  20. Constantinides VC, Paraskevas GP, Boufidou F, Bourbouli M, Pyrgelis ES, Stefanis L, et al. CSF Aβ42 and Aβ42/Aβ40 Ratio in Alzheimer's Disease and Frontotemporal Dementias. Diagnostics. 2023;13(4).
  21. Constantinides VC, Boufidou F, Bourbouli M, Pyrgelis ES, Ghika A, Koros C, et al. Application of the AT(N) and Other CSF Classification Systems in Behavioral Variant Frontotemporal Dementia. Diagnostics (Basel). 2023;13(3).
  22. Boufidou F, Vakrakou AG, Anagnostouli M, Stefanis L, Evangelopoulos ME. An Updated Evaluation of Intrathecal IgG Synthesis Markers in Relation to Oligoclonal Bands. Diagnostics (Basel). 2023 Jan 20;13(3):389.
  23. Boufidou F, Medić S, Lampropoulou V, Siafakas N, Tsakris A, Anastassopoulou C. SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic. Int J Mol Sci. 2023 Aug 19;24(16):12962

 

1ST DEPARTMENT OF NEUROLOGY: