Clinical Neuroanatomy and Biobanking

Human brain morphology and cellular mechanisms in aging and disease

The research team Clinical Neuroanatomy and Biobanking (CNAB) studies human brain morphology, neuroanatomical circuits and cellular disease mechanisms in aging and disease. The research team works closely with clinical, academic and industry partners to advance translational fundamental knowledge to clinical diagnostic tools, develop and apply state-of-the art optical, cellular imaging and MRI techniques and identify novel therapeutic strategies for Parkinson’s disease and related disorders.

Mission statement

To advance our understanding of human brain morphology, brain circuits and cellular disease mechanisms and translate this knowledge into novel diagnostic tools and therapeutic strategies to slow down or halt disease progression in Parkinson’s disease and related neurodegenerative disorders.

We aim to study human brain morphology and neuropathological lesions in postmortem brain tissue of aged individuals and patients with Parkinson’s disease, Dementia with Lewy bodies and Alzheimer’s disease in 3D at macro-, meso-, micro- and nanoscale using advanced imaging methods such as structural and diffusion MRI, 3D CLSM, STED, CLEM, and proximity ligation assays. Within our studies, we focus on understanding (i) the physiological and pathological role of alpha-synuclein and its interactors in GBA-related and sporadic Parkinson’s disease, ii) identification of tissue, biochemical and molecular biomarkers reflecting disease mechanisms in Parkinson’s disease (iii) the pathological sensitivity of MRI outcome measures in Alzheimer’s and Parkinson’s disease and their promise as imaging biomarkers. In close collaboration with the Netherlands Brain bank, we collect and process high-quality brain and skin tissue of well-characterized Parkinson’s patients and Dementia with Lewy bodies for optical and molecular imaging and to study genotype-phenotype correlations.

Together with dept of Radiology and Pathology, we founded the ‘Normal Aging Brain Collection Amsterdam’ in 2014, which aims to collect post-mortem 3T and 7T postmortem quantitative MRI and brain tissue to study age-related and disease-specific signatures in the same patient from macro- to microscale and advance translational neuroscience. Postmortem MRI datasets and brain tissue are available to the scientific community through a Material Transfer Agreement. For more information please visit the NABCA website (http://nabca.eu).

In close collaboration with LUMC and TU Delft, we setup a large multicenter longitudinal observational study ‘Profiling Parkinson’s disease’ (ProPARK) to identify molecular profiles underlying disease severity, progression and adverse drug reactions and translate this knowledge into biomarker panels for next clinical trials. Annual clinical, biospecimen (blood, faeces and skin biopsies) and biannual kinematic data will be collected from 1250 Parkinson patients and 365 controls in the next three years by UMCs and peripheral hospitals in the Netherlands. In addition, we are involved in biobanking and biomarker analysis for clinical studies, for example ‘High Intensity Interval Training Parkinson’s disease’ (HIIT-PD), aiming to modify disease progression in Parkinson’s disease at Amsterdam UMC.

Vision

The primary innovative character provided by Clinical Neuroanatomy and Biobanking (CNAB) is to develop a cutting-edge research infrastructure to study morphology, neuroanatomical circuits and cellular mechanisms in the human brain allowing translational research and advance knowledge aiming to define novel treatment strategies to slow down or halt Parkinson’s disease.

Core facilities and biobanks

“A more holistic, integrated, multidimensional view on the brain, emphasizing it as a system rather than as a collection of single cells or molecules, will allow scientists to go beyond traditional views”

 

Team members

Technical innovation and expertise

  • John Bol, Bsc (senior technician, lab head, operator Perkin Elmer slide scanner)
  • Allert Jonker, Bsc (senior technician, operator Nikon A1R microscope)
  • Evelien Timmermans, Bsc (senior technician, database manager NABCA, operator SP8-STED microscope)
  • Yvon Galis, Bsc (senior technician, NABCA biobank lab)
  • Angela Ingrassia, Msc (senior technician, molecular biology)
  • John Breve, Bsc (senior technician, biochemistry)

NABCA post-mortem MRI and autopsy team

  • Piet Bouman, MSc
  • Max Laansma, MSc
  • Julia Jelgerhuis, Bsc
  • Chen-Pei Lin, MSc
  • Sjoerd Dingerink, Bsc
  • Mark Dubbeldam, MSc
  • Irene Frigerio, MSc
  • Bram van der Gaag, Msc
  • Tino Morella, MSc

Alumni Msc, PhD students and team members

  • Tim Moors, PhD (postdoc, Harvard University, USA)
  • Leonie Vergouw, PhD (ErasmusMC, Rotterdam)
  • Arlin Keo, PhD (LUMC, Leiden)
  • Christina Maat, BSc (Msc, ETH Zurich)
  • Sarah Shahmoradian, PhD (postdoc, C-CINA, Basel)
  • Martijn Steenwijk, PhD (postdoc, KNW, Amsterdam UMC)
  • Nour Majbour, PhD (assistant professor HBKU, Qatar)
  • Yvonne de Gier, Msc (PhD student, RadboudUMC, Amsterdam UMC)
  • Pieter Voorn, PhD (associate professor, Amsterdam UMC)
  • Karin van Dijk, MD, PhD (neurologist, SEIN, Amsterdam)
  • Anke Dijkstra, PhD (postdoc, pathology, Amsterdam UMC)

Key references

Boon BDC, Bulk M, Jonker AJ, Morrema THJ, et al., van de Berg WDJ, Rozemuller AJM, Hoozemans JJM. The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer’s disease. Acta Neuropathol. 2020 Sep 14. doi: 10.1007/s00401-020-02198-8. Epub ahead of print. PMID: 32926214.

Shahmoradian SH, Lewis AJ, Genoud C, et al. Britschgi M, Stahlberg H, Van de Berg WDJ, Lauer ME. Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nat Neurosci. 2019 Jul;22(7):1099-1109. doi: 10.1038/s41593-019-0423-2. Epub 2019 Jun 24. PMID: 31235907.

Fathy YY, Hepp DH, de Jong FJ, Geurts JJG, Foncke EMJ, Berendse HW, van de Berg WDJ, Schoonheim MM. Anterior insular network disconnection and cognitive impairment in Parkinson’s disease. Neuroimage Clin. 2020 Jul 25;28:102364. doi: 10.1016/j.nicl.2020.102364. Epub ahead of print. PMID: 32781423; PMCID: PMC7417948.

Geut H, Hepp DH, Foncke E, Berendse HW, Rozemuller JM, Huitinga I, van de Berg WDJ. Neuropathological correlates of parkinsonian disorders in a large Dutch autopsy series. Acta Neuropathol Commun. 2020 Mar 26;8(1):39. doi: 10.1186/s40478-020-00914-9. PMID: 32216828; PMCID: PMC7098103.

Jonkman LE, Graaf YG, Bulk M, Kaaij E, Pouwels PJW, Barkhof F, Rozemuller AJM, van der Weerd L, Geurts JJG, van de Berg WDJ. Normal Aging Brain Collection Amsterdam (NABCA): A comprehensive collection of postmortem high-field imaging, neuropathological and morphometric datasets of non-neurological controls. Neuroimage Clin. 2019;22:101698. doi: 10.1016/j.nicl.2019.101698. Epub 2019 Jan 29. PMID: 30711684; PMCID: PMC6360607.

Quadri M, Mandemakers W, Grochowska MM, et al. van de Berg WDJ, Bonifati V; International Parkinsonism Genetics Network. LRP10 genetic variants in familial Parkinson’s disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study. Lancet Neurol. 2018 Jul;17(7):597-608. doi: 10.1016/S1474-4422(18)30179-0. Epub 2018 Jun 7. Erratum in: Lancet Neurol. 2020 Feb;19(2):e2. PMID: 29887161.

Oosterveld LP, Verberk IMW, Majbour NK, El-Agnaf OM, Weinstein HC, Berendse HW, Teunissen CE, van de Berg WDJ. CSF or serum neurofilament light added to α-Synuclein panel discriminates Parkinson’s from controls. Mov Disord. 2020 Feb;35(2):288-295. doi: 10.1002/mds.27897. Epub 2019 Nov 18. PMID: 31737952; PMCID: PMC7027879.

Keo A, Mahfouz A, Ingrassia AMT, Meneboo JP, Villenet C, Mutez E, Comptdaer T, Lelieveldt BPF, Figeac M, Chartier-Harlin MC, van de Berg WDJ, van Hilten JJ, Reinders MJT. Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease. Commun Biol. 2020 Mar 5;3(1):101. doi: 10.1038/s42003-020-0804-9. PMID: 32139796; PMCID: PMC7058608.

 

Publications