Neurochemistry of Neurodegeneration

Research is focused on the neurochemistry of neurodegenerative disorders, specifically movement disorders (e.g. Parkinson’s disease, and related disorders, including parkinsonism and pediatric movement neurotransmitter movement disorders) and dementia syndromes (e.g.  cerebral amyloid angiopathy [CAA], Alzheimer’s disease and related disorders).

In our research we aim to obtain a closer understanding of the pathophysiological mechanisms of neurodegenerative disorders. In this research, the aggregation of disease-related proteins, the interaction of these proteins with other proteins and with cells in the brain, inflammatory reactions associated with the accumulation of these pathogenic proteins and routes for clearance of amyloidogenic proteins from the brain is studied.

The aim is to translate novel insights from pathofysiological studies into biomarkers of disease. Novel candidate biomarkers are identified through screening techniques (such as proteomics) or from new insights into the underlying pathophysiology. The biomarkers mainly comprise proteins, enzymes and metabolites that each have a specific relation to a disease. Therefore, we work on the development and validation of biomarkers in body fluids (especially cerebrospinal fluid) for diagnosis and prognosis of these disorders; The group collaborates with clinicians within the Parkinson Centre Nijmegen and the Radboud Alzheimer Centre to reach this goal as well as with many (inter)national researchers. A large biobank with cerebrospinal fluid and blood samples from patients with many different types of neurological disorders has been established to support this research. Marcel Verbeek also leads the national reference centre for specialized CSF diagnostics. It allows him to immediately translate and implement novel biomarker assays in the routine diagnostic work-up of neurological disorders and offer these to clinicians at other institutes. These biomarkers will create personalized value for diagnostic or prognostic purposes. Novel insights into disease mechanisms may also lead to the development of tailor-made therapies, that can be monitored using biomarkers, and therefore, his approach of the combination of basic and translational neurosciences contributes to personalized health care.

Key publications 2017 below; for a complete list of publications, click here

Kuiperij HB, Versleijen AA, Beenes M, Verwey NA, Benussi L, Paterlini A, Binetti G, Teunissen CE, Raaphorst J, Schelhaas HJ, Küsters B, Pijnenburg YA, Ghidoni R, Verbeek MM. Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes: A Pilot Study. J Alzheimers Dis. 2017;55(2):585-595.

van Etten ES, Verbeek MM, van der Grond J, Zielman R, van Rooden S, van Zwet EW, van Opstal AM, Haan J, Greenberg SM, van Buchem MA, Wermer MJ, Terwindt GM. β-Amyloid in CSF: Biomarker for preclinical cerebral amyloid angiopathy. Neurology. 2017;88(2):169-176.

Wassenberg T, Molero-Luis M, Jeltsch K, Hoffmann GF, Assmann B, Blau N, Garcia-Cazorla A, Artuch R, Pons R, Pearson TS, Leuzzi V, Mastrangelo M, Pearl PL, Lee WT, Kurian MA, Heales S, Flint L, Verbeek M, Willemsen M, Opladen T. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis. 2017 J;12(1):12.

van Waalwijk van Doorn LJ, Gispert JD, Kuiperij HB, Claassen JA, Arighi A, Baldeiras I, Blennow K, Bozzali M, Castelo-Branco M, Cavedo E, Emek-Savaş DD, Eren E, Eusebi P, Farotti L, Fenoglio C, Ormaechea JF, Freund-Levi Y, Frisoni GB, Galimberti D, Genc S, Greco V, Hampel H, Herukka SK, Liu Y, Lladó A, Lleó A, Nobili FM, Oguz KK, Parnetti L, Pereira J, Picco A, Pikkarainen M, de Oliveira CR, Saka E, Salvadori N, Sanchez-Valle R, Santana I, Scarpini E, Scheltens P, Soininen H, Tarducci R, Teunissen C, Tsolaki M, Urbani A, Vilaplana E, Visser PJ, Wallin AK, Yener G, Molinuevo JL, Meulenbroek O, Verbeek MM. Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes. J Alzheimers Dis. 2017;56(2):543-555.

Mothapo KM, Ten Oever J, Koopmans P, Stelma FF, Burm S, Bajramovic J, Verbeek MM, Rikkert MG, Netea MG, Koopman G, van der Ven AJ. Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions. J Neurovirol. 2017 Apr;23(2):250-259.

Biemans EALM, Jäkel L, de Waal RMW, Kuiperij HB, Verbeek MM. Limitations of the hCMEC/D3 cell line as a model for Aβ clearance by the human blood-brain barrier. J Neurosci Res. 2017 Jul;95(7):1513-1522.

Willemsen MA, Vissers LE, Verbeek MM, van Bon BW, Geuer S, Gilissen C, Klepper J, Kwint MP, Leen WG, Pennings M, Wevers RA, Veltman JA, Kamsteeg EJ. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome. Eur J Hum Genet. 2017 Jun;25(6):771-774.

van Waalwijk van Doorn LJC, Kulic L, Koel-Simmelink MJA, Kuiperij HB, Versleijen AAM, Struyfs H, Twaalfhoven HAM, Fourier A, Engelborghs S, Perret-Liaudet A, Lehmann S, Verbeek MM, Vanmechelen EJM, Teunissen CE. Multicenter Analytical Validation of Aβ40 Immunoassays. Front Neurol. 2017;8:310. PMID: 28725210.

Jäkel L, Van Nostrand WE, Nicoll JAR, Werring DJ, Verbeek MM. Animal models of cerebral amyloid angiopathy. Clin Sci (Lond). 2017; 131(19):2469-2488. PMID: 28963121235. Banerjee G, Carare R, Cordonnier C, Greenberg SM, Schneider JA, Smith EE, Buchem MV, Grond JV, Verbeek MM, Werring DJ. The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice. J Neurol Neurosurg Psychiatry. 2017PMID: 28844070

Links

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www.caviaproject.nl

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EL UPDATE OCT 2017