IMPRiND Project

Latest news

Publication on eLife

Cryo-EM of two polymorphic structures of alpha-synuclein fibrils by Luc Bousset and Ronald Melki from CNRS has just be published on eLife:. ...

35 years Anniversary

As part of the LMB-365 project, Michel Goedert was recognised this week for 35 years at LMB (The Medical Research Council Laboratory of ...

Post-Brexit scenarios

Regarding the participation of British researchers in Horizon 2020 projects, UK Research and Innovation’s (UKRI) Brussels-based UK ...

Blocking aggregate propagation in neurodegenerative diseases


Blocking aggregate propagation in neurodegenerative diseases IMPRiND – Inhibiting Misfolded protein Propagation In Neurodegenerative Diseases – is an international consortium that aims to map and target critical steps in the propagation of misfolded tau and α-synuclein, considered the main culprits of neurodegeneration in Alzheimer's and Parkinson's disease respectively. Our plans are built upon:
  • Identify disease-relevant misfolded assemblies, imprint their biological properties in vitro and/or in cellulo and generate homogeneous populations in order to assay and interfere with their pathogenic effects.
  • Develop and miniaturise assays to monitor up-take, secretion, clearance and oligomerisation using bimolecular fluorescence complementation of oligomeric species or transfer of untagged assemblies to fluorescently labelled fibril-naïve cells and measure markers of early proteotoxicity that are suitable for high throughput or high content screens.
  • Perform genetic screens based on disease-relevant gene/protein networks and assess druggability of identified targets.
  • Deliver robust validation assays for these molecular events in complex cellular systems with greater functional resemblance to the native milieu of the brain such as iPSC-based models and organotypic cultures or simple model organisms such as Drosophila or zebrafish.
  • Improve existing animal models in order to standardise pathological readouts for in vivo validation of modifiers, correlate them with novel peripheral or in situ markers using microdialysis to accelerate the assessment of therapeutic interventions and relevance to humans, e.g. by transplantation of human iPSC neurons in animals.
In the IMPRiND consortium, we will construct this entire pipeline to examine the propagation of α-synuclein and tau and test their tractability against disease progression.
IMPRIND started in March 2017 and will run until February 2021.

Most recent publications

1.
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.
eLife 8, e48907 (2019). doi:10.7554/eLife.48907
2.
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.
Neurobiology of Disease 129, 38-43 (2019). doi:10.1016/j.nbd.2019.05.002
3.
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-02014-y
4.
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-01995-0
5.
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network.
Stem Cell Reports (2019). doi:10.1016/j.stemcr.2018.12.007
6.
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐ATPase and AMPA receptors.
The EMBO Journal e99871 (2019). doi:10.15252/embj.201899871
7.
α-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities.
Journal of Neurochemistry 150, 522-534 (2019). doi:10.1111/jnc.14808
8.
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons.
Stem Cells International (2019). https://www.hindawi.com/journals/sci/2019/2945435/.
9.
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.
Frontiers in Immunology 10, (2019). doi:10.3389/fimmu.2019.01139
10.
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.
Frontiers in Molecular Neuroscience 12, (2019). doi:10.3389/fnmol.2019.00107
11.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s disease.
bioRxiv 468892 (2018). doi:10.1101/468892
12.
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces.
Scientific Reports 8, 10788 (2018). doi:10.1038/s41598-018-28856-2
13.
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
ACS Chemical Neuroscience 9, 1276-1282 (2018). doi:10.1021/acschemneuro.8b00094
14.
Tau Filaments and the Development of Positron Emission Tomography Tracers.
Frontiers in Neurology 9, (2018). doi:10.3389/fneur.2018.00070
15.
Structures of filaments from Pick’s disease reveal a novel tau protein fold.
Nature 561, 137-140 (2018). doi:10.1038/s41586-018-0454-y
16.
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold.
Acta Neuropathologica 136, 699-708 (2018). doi:10.1007/s00401-018-1914-z
17.
123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson’s disease cohort versus Parkinson’s disease: 123I-FP-CIT IMAGING IN A P.A53T PD COHORT.
Movement Disorders 33, 1734-1739 (2018). doi:10.1002/mds.27451
18.
Neurodegeneration and the ordered assembly of α-synuclein.
Cell and Tissue Research 373, 137-148 (2018). doi:10.1007/s00441-017-2706-9
19.
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease.
Journal of Parkinson’s Disease 7, 569-576 (2017). doi:10.3233/JPD-171176
20.
Cryo-EM structures of tau filaments from Alzheimer’s disease.
Nature 547, 185-190 (2017). doi:10.1038/nature23002
21.
How is alpha-synuclein cleared from the cell?.
Journal of Neurochemistry doi:10.1111/jnc.14704

1.
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.
eLife 8, e48907 (2019). doi:10.7554/eLife.48907
2.
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.
Neurobiology of Disease 129, 38-43 (2019). doi:10.1016/j.nbd.2019.05.002
3.
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-02014-y
4.
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-01995-0
5.
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network.
Stem Cell Reports (2019). doi:10.1016/j.stemcr.2018.12.007
6.
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐ATPase and AMPA receptors.
The EMBO Journal e99871 (2019). doi:10.15252/embj.201899871
7.
α-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities.
Journal of Neurochemistry 150, 522-534 (2019). doi:10.1111/jnc.14808
8.
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons.
Stem Cells International (2019). https://www.hindawi.com/journals/sci/2019/2945435/.
9.
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.
Frontiers in Immunology 10, (2019). doi:10.3389/fimmu.2019.01139
10.
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.
Frontiers in Molecular Neuroscience 12, (2019). doi:10.3389/fnmol.2019.00107
11.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s disease.
bioRxiv 468892 (2018). doi:10.1101/468892
12.
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces.
Scientific Reports 8, 10788 (2018). doi:10.1038/s41598-018-28856-2
13.
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
ACS Chemical Neuroscience 9, 1276-1282 (2018). doi:10.1021/acschemneuro.8b00094
14.
Tau Filaments and the Development of Positron Emission Tomography Tracers.
Frontiers in Neurology 9, (2018). doi:10.3389/fneur.2018.00070
15.
Structures of filaments from Pick’s disease reveal a novel tau protein fold.
Nature 561, 137-140 (2018). doi:10.1038/s41586-018-0454-y
16.
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold.
Acta Neuropathologica 136, 699-708 (2018). doi:10.1007/s00401-018-1914-z
17.
123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson’s disease cohort versus Parkinson’s disease: 123I-FP-CIT IMAGING IN A P.A53T PD COHORT.
Movement Disorders 33, 1734-1739 (2018). doi:10.1002/mds.27451
18.
Neurodegeneration and the ordered assembly of α-synuclein.
Cell and Tissue Research 373, 137-148 (2018). doi:10.1007/s00441-017-2706-9
19.
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease.
Journal of Parkinson’s Disease 7, 569-576 (2017). doi:10.3233/JPD-171176
20.
Cryo-EM structures of tau filaments from Alzheimer’s disease.
Nature 547, 185-190 (2017). doi:10.1038/nature23002
21.
How is alpha-synuclein cleared from the cell?.
Journal of Neurochemistry doi:10.1111/jnc.14704

1.
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.
eLife 8, e48907 (2019). doi:10.7554/eLife.48907
2.
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.
Neurobiology of Disease 129, 38-43 (2019). doi:10.1016/j.nbd.2019.05.002
3.
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-02014-y
4.
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-01995-0
5.
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network.
Stem Cell Reports (2019). doi:10.1016/j.stemcr.2018.12.007
6.
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐ATPase and AMPA receptors.
The EMBO Journal e99871 (2019). doi:10.15252/embj.201899871
7.
α-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities.
Journal of Neurochemistry 150, 522-534 (2019). doi:10.1111/jnc.14808
8.
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons.
Stem Cells International (2019). https://www.hindawi.com/journals/sci/2019/2945435/.
9.
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.
Frontiers in Immunology 10, (2019). doi:10.3389/fimmu.2019.01139
10.
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.
Frontiers in Molecular Neuroscience 12, (2019). doi:10.3389/fnmol.2019.00107
11.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s disease.
bioRxiv 468892 (2018). doi:10.1101/468892
12.
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces.
Scientific Reports 8, 10788 (2018). doi:10.1038/s41598-018-28856-2
13.
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
ACS Chemical Neuroscience 9, 1276-1282 (2018). doi:10.1021/acschemneuro.8b00094
14.
Tau Filaments and the Development of Positron Emission Tomography Tracers.
Frontiers in Neurology 9, (2018). doi:10.3389/fneur.2018.00070
15.
Structures of filaments from Pick’s disease reveal a novel tau protein fold.
Nature 561, 137-140 (2018). doi:10.1038/s41586-018-0454-y
16.
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold.
Acta Neuropathologica 136, 699-708 (2018). doi:10.1007/s00401-018-1914-z
17.
123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson’s disease cohort versus Parkinson’s disease: 123I-FP-CIT IMAGING IN A P.A53T PD COHORT.
Movement Disorders 33, 1734-1739 (2018). doi:10.1002/mds.27451
18.
Neurodegeneration and the ordered assembly of α-synuclein.
Cell and Tissue Research 373, 137-148 (2018). doi:10.1007/s00441-017-2706-9
19.
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease.
Journal of Parkinson’s Disease 7, 569-576 (2017). doi:10.3233/JPD-171176
20.
Cryo-EM structures of tau filaments from Alzheimer’s disease.
Nature 547, 185-190 (2017). doi:10.1038/nature23002
21.
How is alpha-synuclein cleared from the cell?.
Journal of Neurochemistry doi:10.1111/jnc.14704

1.
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.
eLife 8, e48907 (2019). doi:10.7554/eLife.48907
2.
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.
Neurobiology of Disease 129, 38-43 (2019). doi:10.1016/j.nbd.2019.05.002
3.
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-02014-y
4.
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-01995-0
5.
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network.
Stem Cell Reports (2019). doi:10.1016/j.stemcr.2018.12.007
6.
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐ATPase and AMPA receptors.
The EMBO Journal e99871 (2019). doi:10.15252/embj.201899871
7.
α-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities.
Journal of Neurochemistry 150, 522-534 (2019). doi:10.1111/jnc.14808
8.
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons.
Stem Cells International (2019). https://www.hindawi.com/journals/sci/2019/2945435/.
9.
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.
Frontiers in Immunology 10, (2019). doi:10.3389/fimmu.2019.01139
10.
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.
Frontiers in Molecular Neuroscience 12, (2019). doi:10.3389/fnmol.2019.00107
11.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s disease.
bioRxiv 468892 (2018). doi:10.1101/468892
12.
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces.
Scientific Reports 8, 10788 (2018). doi:10.1038/s41598-018-28856-2
13.
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
ACS Chemical Neuroscience 9, 1276-1282 (2018). doi:10.1021/acschemneuro.8b00094
14.
Tau Filaments and the Development of Positron Emission Tomography Tracers.
Frontiers in Neurology 9, (2018). doi:10.3389/fneur.2018.00070
15.
Structures of filaments from Pick’s disease reveal a novel tau protein fold.
Nature 561, 137-140 (2018). doi:10.1038/s41586-018-0454-y
16.
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold.
Acta Neuropathologica 136, 699-708 (2018). doi:10.1007/s00401-018-1914-z
17.
123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson’s disease cohort versus Parkinson’s disease: 123I-FP-CIT IMAGING IN A P.A53T PD COHORT.
Movement Disorders 33, 1734-1739 (2018). doi:10.1002/mds.27451
18.
Neurodegeneration and the ordered assembly of α-synuclein.
Cell and Tissue Research 373, 137-148 (2018). doi:10.1007/s00441-017-2706-9
19.
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease.
Journal of Parkinson’s Disease 7, 569-576 (2017). doi:10.3233/JPD-171176
20.
Cryo-EM structures of tau filaments from Alzheimer’s disease.
Nature 547, 185-190 (2017). doi:10.1038/nature23002
21.
How is alpha-synuclein cleared from the cell?.
Journal of Neurochemistry doi:10.1111/jnc.14704

1.
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.
eLife 8, e48907 (2019). doi:10.7554/eLife.48907
2.
Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.
Neurobiology of Disease 129, 38-43 (2019). doi:10.1016/j.nbd.2019.05.002
3.
Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-02014-y
4.
LRRK2 modifies α-syn pathology and spread in mouse models and human neurons.
Acta Neuropathologica (2019). doi:10.1007/s00401-019-01995-0
5.
Propagation of α-Synuclein Strains within Human Reconstructed Neuronal Network.
Stem Cell Reports (2019). doi:10.1016/j.stemcr.2018.12.007
6.
Clustering of Tau fibrils impairs the synaptic composition of α3‐Na+/K+‐ATPase and AMPA receptors.
The EMBO Journal e99871 (2019). doi:10.15252/embj.201899871
7.
α-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities.
Journal of Neurochemistry 150, 522-534 (2019). doi:10.1111/jnc.14808
8.
Pharmacological Transdifferentiation of Human Nasal Olfactory Stem Cells into Dopaminergic Neurons.
Stem Cells International (2019). https://www.hindawi.com/journals/sci/2019/2945435/.
9.
The Role of Antibodies and Their Receptors in Protection Against Ordered Protein Assembly in Neurodegeneration.
Frontiers in Immunology 10, (2019). doi:10.3389/fimmu.2019.01139
10.
Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.
Frontiers in Molecular Neuroscience 12, (2019). doi:10.3389/fnmol.2019.00107
11.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s disease.
bioRxiv 468892 (2018). doi:10.1101/468892
12.
Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces.
Scientific Reports 8, 10788 (2018). doi:10.1038/s41598-018-28856-2
13.
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
ACS Chemical Neuroscience 9, 1276-1282 (2018). doi:10.1021/acschemneuro.8b00094
14.
Tau Filaments and the Development of Positron Emission Tomography Tracers.
Frontiers in Neurology 9, (2018). doi:10.3389/fneur.2018.00070
15.
Structures of filaments from Pick’s disease reveal a novel tau protein fold.
Nature 561, 137-140 (2018). doi:10.1038/s41586-018-0454-y
16.
Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold.
Acta Neuropathologica 136, 699-708 (2018). doi:10.1007/s00401-018-1914-z
17.
123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson’s disease cohort versus Parkinson’s disease: 123I-FP-CIT IMAGING IN A P.A53T PD COHORT.
Movement Disorders 33, 1734-1739 (2018). doi:10.1002/mds.27451
18.
Neurodegeneration and the ordered assembly of α-synuclein.
Cell and Tissue Research 373, 137-148 (2018). doi:10.1007/s00441-017-2706-9
19.
A Critical Assessment of Exosomes in the Pathogenesis and Stratification of Parkinson’s Disease.
Journal of Parkinson’s Disease 7, 569-576 (2017). doi:10.3233/JPD-171176
20.
Cryo-EM structures of tau filaments from Alzheimer’s disease.
Nature 547, 185-190 (2017). doi:10.1038/nature23002
21.
How is alpha-synuclein cleared from the cell?.
Journal of Neurochemistry doi:10.1111/jnc.14704

Latest news

Publication on eLife

Cryo-EM of two polymorphic structures of alpha-synuclein fibrils by Luc Bousset and Ronald Melki from CNRS has just be published on eLife:. ...

35 years Anniversary

As part of the LMB-365 project, Michel Goedert was recognised this week for 35 years at LMB (The Medical Research Council Laboratory of ...

Post-Brexit scenarios

Regarding the participation of British researchers in Horizon 2020 projects, UK Research and Innovation’s (UKRI) Brussels-based UK ...

This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking (www.imi.europa.eu) under grant agreement No 116060. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 17.00038.

The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.