Research group Translational research neurodegenerative disorders

Aims

1. We want to identify novel biomarkers of disease for diagnostic and monitoring purposes.
2. We aim to continue fundamental research in mechanisms of neurodegeneration in order to translate these findings to define novel biomarkers of disease.
3. We aim to broaden our research to biomarkers of extracerebral processes relevant for neurodegenerative disorders.

We aim to perform three types of studies to reach this ambition.

• 1. Identify novel biomarkers

  We want to identify novel biomarkers of disease for diagnostic and monitoring purposes.

  Whereas protein aggregation biomarkers are already available for clinical applications, we aim to extend this panel to biomarkers of cerebral vascular function and neuroinflammation. Together with genetic susceptibility and neuroimaging biomarkers, these will allow advanced phenotyping and will form the basis for personalized therapy. For this, we will continue our efforts to create unique patient cohorts and biobanks that are crucial to laboratory-supported phenotyping. Moreover, we will continue to embrace novel technologies (such as metabolomics, glycomics, big data analyses).

• 2. Continue fundamental research

  We aim to continue fundamental research in mechanisms of neurodegeneration in order to translate these findings to define novel biomarkers of disease.

• 3. Broaden our research

  We will broaden our research to biomarkers of extracerebral processes. In Parkinson's disease, systemic inflammation, systemic drug-metabolizing enzymes and the gut microbiome are important modifiers of both disease development, progression and the effectiveness of levodopa treatment. These systemic biomarkers will aid clinical decisions on personalized drug use, enhancing quality of life of patients.

Achievements

• Cerebral Amyloid Angiopathy (CAA)

  We were the first research group to demonstrate that Cerebral Amyloid Angiopathy (CAA) is characterized by a specific pattern of low cerebrospinal fluid levels of various amyloid beta proteins, which has now become a standard characterization of patients with CAA worldwide.

• More than one form of CAA

  We have recently demonstrated that more than one (molecularly defined) form of CAA exists depending on its origin (sporadic vs. Alzheimer-associated vs. immunotherapy-associated CAA), which is relevant to future therapeutic interventions.

• Peripheral levodopa resistance in Parkinson

  We were the first research group to report on the inducing effect of levodopa on dopa decarboxylase levels in Parkinson patients, based on which we coined the novel concept of 'peripheral levodopa resistance in Parkinson'.

Publications

See the publication list of the research group leader on Web of Science.

• A selection of our publications

  • Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis. Jäkel L, De Kort AM, Klijn CJM, Schreuder FHBM, Verbeek MM. Alzheimers Dement. 2022; 18(1):10-28. 
  • Decreased microvascular claudin-5 levels in cerebral amyloid angiopathy associated with intracerebral haemorrhage. Jäkel L, Claassen KKWJ, De Kort AM, Jolink WMT, Vermeiren Y, Schreuder FHBM, Küsters B, Klijn CJM, Kuiperij HB, Verbeek MM.. Brain Pathol. 2024 Nov;34(6):e13270. 
  • Altered brain expression and cerebrospinal fluid levels of TIMP4 in cerebral amyloid angiopathy. Jäkel L, De Kort AM, Stellingwerf A, Hernández Utrilla C, Kersten I, Vervuurt M, Vermeiren Y, Küsters B, Schreuder FHBM, Klijn CJM, Kuiperij HB, Verbeek MM. Acta Neuropathol Commun. 2024 Jun 24;12(1):103. 
  • α-Synuclein real-time quaking-induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism. van Rumund A, Green AJE, Fairfoul G, Esselink RAJ, Bloem BR, Verbeek MM. Ann Neurol. 2019 May;85(5):777-781
  • Normal cerebrospinal fluid concentrations of PDGFRβ in patients with cerebral amyloid angiopathy and Alzheimer's disease. De Kort AM, Kuiperij HB, Kersten I, Versleijen AAM, Schreuder FHBM, Van Nostrand WE, Greenberg SM, Klijn CJM, Claassen JAHR, Verbeek MM. Alzheimers Dement. 2022 Oct;18(10):1788-1796.
  • No replicating evidence for anti-amyloid-β autoantibodies in cerebral amyloid angiopathy-related inflammation. van den Berg E, Roelofs R, Jäkel L, Greenberg SM, Charidimou A, van Etten ES, Boche D, Klijn CJM, Schreuder FHBM, Kuiperij HB, Verbeek MM. Ann Clin Transl Neurol. 2024 Oct;11(10):2563-2571. 
  • Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy. De Kort AM, Kuiperij HB, Marques TM, Jäkel L, van den Berg E, Kersten I, van Berckel-Smit HEP, Duering M, Stoops E, Abdo WF, Rasing I, Voigt S, Koemans EA, Kaushik K, Warren AD, Greenberg SM, Brinkmalm G, Terwindt GM, Wermer MJH, Schreuder FHBM, Klijn CJM, Verbeek MM. Ann Neurol. 2023 Jun;93(6):1173-1186.
  • Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase. van Rumund A, Pavelka L, Esselink RAJ, Geurtz BPM, Wevers RA, Mollenhauer B, Krüger R, Bloem BR, Verbeek MM. NPJ Parkinsons Dis. 2021 Mar 19;7(1):29.
  • Mechanisms of peripheral levodopa resistance in Parkinson's disease. Beckers M, Bloem BR, Verbeek MM. NPJ Parkinsons Dis. 2022 May 11;8(1):56.
  • Cerebrospinal fluid shotgun proteomics identifies distinct proteomic patterns in cerebral amyloid angiopathy rodent models and human patients. Vervuurt M, Schrader JM, de Kort AM, Kersten I, Wessels HJCT, Klijn CJM, Schreuder FHBM, Kuiperij HB, Gloerich J, Van Nostrand WE, Verbeek MM. Acta Neuropathol Commun. 2024;12(1):6.