The Generative Brain

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf

The Institute of Neuropathology is an institute of the University Medical Center Hamburg-Eppendorf (UKE). UKE itself is a public-law corporation with legal capacity, set up by a Hamburg state law of 2001 as a constituent body of the University of Hamburg, so the institute has no separate legal personality. Markus Glatzel, a neuropathologist, has directed it since 2006. Its prion work centres on one mechanism: ADAM10 cuts the prion protein (PrP) off the cell surface, a process called shedding, and the released soluble PrP appears to be protective. The group led by Hermann Altmeppen has shown that ADAM10 is the only relevant PrP sheddase, has made antibodies that recognise the shed form in human tissue, and is asking two applied questions: whether shed PrP in spinal fluid or blood could serve as a biomarker, and whether shedding can be stimulated with PrP-binding antibodies or ligands as a therapy. Funding comes from the DFG, through the Kiel and Hamburg collaborative research centre SFB 877 and a 2020 to 2025 research grant, from repeated CJD Foundation grants, and from UKE and private foundations. In the last 12 months the institute has co-authored a mouse study on the D178N mutation that underlies some genetic prion diseases, a UKE-led prion mouse treatment study and a tau seeding study with the Goettingen reference center.

Key facts

  • UKE is a public-law corporation with legal capacity and the status of a constituent body of the University of Hamburg, seated in Hamburg, under a Hamburg state law of 12 September 2001 last amended 18 December 2020; it is governed by a Kuratorium chaired by the supervising ministry and a Vorstand led by the Medical Director that includes the Dean.
  • Markus Glatzel is institute director and medical head; he has been professor of neuropathology at UKE since 2006, chair of the UKE Diagnostic Center since 2011 and editor-in-chief of Brain Pathology since 2019.
  • The core prion programme is ADAM10-mediated shedding of PrP: a 2018 UKE-led paper introduced an antibody against the shed PrP neo-epitope and showed that ADAM10 is the exclusive PrP sheddase in the nervous system and that glycosylation and membrane anchor type shape shedding.
  • A 2024 Acta Neuropathologica paper identified PrP cut at tyrosine 226 as the physiological ADAM10-dependent shed form in humans and found that shed PrP relocates to misfolded protein deposits in human and animal prion disease and in Alzheimer disease.
  • The therapeutic idea is to increase shedding: a 2021 Science Advances paper showed that PrP-binding ligands raise PrP release in cells and brain slice cultures, and a DFG research grant running 2020 to 2025 tested antibody and ligand-based stimulation of shedding as a treatment strategy.
  • The DFG funded the shedding work through SFB 877, Proteolysis as a regulatory event in pathophysiology, a Kiel and Hamburg collaborative research centre; Altmeppen joined it in 2014 with subproject A12, which Glatzel led from 2018.
  • The CJD Foundation has funded the group repeatedly: a 2016 to 2017 grant on targeting PrP processing as therapy, a 2018 grant on the neuroprotective N1 fragment of PrP, and the 2022 Andy Lewis Memorial Grant on shed PrP as a biomarker in spinal fluid or blood and as a therapeutic target; no amounts are published.
  • Other funders acknowledged on the shedding papers are the Werner-Otto-Stiftung, the Alzheimer Forschung Initiative, the DFG research training group GRK1459 and UKE internal funds.
  • In February 2026 Altmeppen co-authored, with Milan, Rome, NIAID Hamilton and CIC bioGUNE groups, a study finding that mice carrying the D178N PrP mutation did not produce infectious prions, and that RML prions passed through D178N PrP gained new strain features that do not match FFI or CJD178.
  • In January 2026 a UKE-led study (senior author Krasemann) reported that oral mGluR5 inhibitors given before symptoms prolonged survival in prion-infected mice without lowering PrPRes, while treatment after onset did not help; it was funded in part by NIA grants and UKE.
  • The institute works with the Goettingen National Reference Center for TSE: joint papers include the 2021 Science Advances ligand study, the 2024 human shed PrP paper and a December 2025 Brain Pathology study of tau seeding in rapidly progressive Alzheimer disease.
  • No page opened describes a clinical, diagnostic or counselling service of the institute for prion disease patients or families; its documented prion output is laboratory research and publications.

Timeline

  1. 2001Hamburg law establishes UKE as a public-law corporation and constituent body of the University of Hamburg.
  2. 2006Glatzel becomes director of the Institute of Neuropathology.
  3. 2014Altmeppen joins SFB 877 with subproject A12 on ADAM10-mediated PrP shedding.
  4. 2016Start of a CJD Foundation grant to Altmeppen on targeting PrP processing as therapy, running to 2017.
  5. 2018Glatzel takes over SFB 877 subproject A12; Altmeppen receives a CJD Foundation grant on the N1 fragment of PrP.
  6. 2018Molecular Neurodegeneration paper establishing ADAM10 as the exclusive PrP sheddase in the nervous system.
  7. 2020Start of the DFG research grant on antibody and ligand-based stimulation of PrP shedding, running to 2025.
  8. 2021Science Advances paper showing PrP-binding ligands induce PrP shedding.
  9. 2022Altmeppen receives the CJD Foundation Andy Lewis Memorial Grant for shed PrP as biomarker and therapeutic target.
  10. 2023Cell and Tissue Research review on ADAM10-mediated shedding of PrP.
  11. 2024Acta Neuropathologica paper identifying human PrP shedding at Y226 by ADAM10.
  12. 2025Neural Regeneration Research review on proteolytic shedding of PrP by the Altmeppen group, published online.
  13. 2025Brain Pathology paper with the Goettingen reference center on tau seeding in rapidly progressive Alzheimer disease, published online.
  14. 2026Acta Neuropathologica Communications paper from the institute on presymptomatic mGluR5 inhibition in a prion mouse model.
  15. 2026Acta Neuropathologica paper with Altmeppen on D178N PrP transgenic mice and RML strain properties, with NIAID Hamilton and CIC bioGUNE co-authors.
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