A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies
Collectively our study demonstrates the accumulation of seed-competent pathological nuclear associated aSyn, alongside nuclear DNA damage and the potential involvement of DNA damage derived cytoDNA species in cytoplasmic aSyn pathology. Ultimately, our study supports the hypothesis of a reciprocal relationship between aSyn pathology and nuclear DNA damage and highlights a potential underlying role for DNA damage in pathological mechanisms relevant to DLB, as well as other synucleinopathies, opening novel possibilities for diagnosis and treatment.
Authors
- David J. Koss (ORCID: https://orcid.org/0000-0002-8034-9880)
- Tiago F. Outeiro (ORCID: https://orcid.org/0000-0003-1679-1727)
- Andrew C.G. Porter (ORCID: https://orcid.org/0000-0002-6954-3041)
- Paweł Palmowski (ORCID: https://orcid.org/0000-0001-9163-9560)
- B. F. GRAHAM
- Daniel Erskine (ORCID: https://orcid.org/0000-0002-1752-5343)
- Fiona E. N. LeBeau (ORCID: https://orcid.org/0000-0003-1453-4022)
- Lauren Walker (ORCID: https://orcid.org/0000-0001-8281-8938)
- Hariharan Menon
- Nicola Morrice (ORCID: https://orcid.org/0000-0003-0165-8376)
- Omar M. A. El‐Agnaf (ORCID: https://orcid.org/0000-0002-6850-8084)
- Johannes Attems (ORCID: https://orcid.org/0000-0003-1636-1700)
- Simona S. Ghanem (ORCID: https://orcid.org/0000-0003-4164-6353)
- Olivia Todd
- Zoe Anderson
- Tamsin Yang
- L. Findlay
Institutions
- University of Dundee (GB)
- German Center for Neurodegenerative Diseases (DE)
- Max Planck Institute for the Study of Religious and Ethnic Diversity (DE)
- Universitätsmedizin Göttingen (DE)
- Hamad bin Khalifa University (QA)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- Newcastle University (GB)
- Qatar Foundation (QA)
Publication Details
- Journal
- Molecular Neurodegeneration
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1186/s13024-025-00813-4
- Citations
- 4
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.56
Funders
- Alzheimer’s Research UK