Connectomics and molecular imaging in neurodegeneration

Abstract

Our understanding on human neurodegenerative disease was previously limited to clinical data and inferences about the underlying pathology based on histopathological examination. Animal models and in vitro experiments have provided evidence for a cell-autonomous and a non-cell-autonomous mechanism for the accumulation of neuropathology. Combining modern neuroimaging tools to identify distinct neural networks (connectomics) with target-specific positron emission tomography (PET) tracers is an emerging and vibrant field of research with the potential to examine the contributions of cell-autonomous and non-cell-autonomous mechanisms to the spread of pathology. The evidence provided here suggests that both cell-autonomous and non-cell-autonomous processes relate to the observed in vivo characteristics of protein pathology and neurodegeneration across the disease spectrum. We propose a synergistic model of cell-autonomous and non-cell-autonomous accounts that integrates the most critical factors (i.e., protein strain, susceptible cell feature and connectome) contributing to the development of neuronal dysfunction and in turn produces the observed clinical phenotypes. We believe that a timely and longitudinal pursuit of such research programs will greatly advance our understanding of the complex mechanisms driving human neurodegenerative diseases.

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Acknowledgements

Faculty of the Multimodal Imaging in Neurodegeneration Cologne (MINC) symposium

Funding

The Molecular Imaging of Neurodegeneration Cologne (MINC) Symposium was partly funded by the Deutsche Forschungsgemeinschaft (DFG) awarded to Dr. Thilo van Eimeren (EI 892/5–1). The Deutsche Forschungsgemeinschaft (DFG) also awarded funding to Dr. Alexander Drzezga (DR 442/91).

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Correspondence to Gérard N. Bischof.

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Bischof, G.N., Ewers, M., Franzmeier, N. et al. Connectomics and molecular imaging in neurodegeneration. Eur J Nucl Med Mol Imaging 46, 2819–2830 (2019). https://doi.org/10.1007/s00259-019-04394-5

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Keywords

  • Multimodal Imaging
  • Proteinpathology
  • Functional Connectivity
  • Pathophysiological Spreading
  • Selective Vulnerability