Date and time
Location
Virtual
Online via Zoom
Rethinking neurodegeneration: Could failing protein clearance provide the missing link?
Recent genome-wide association studies have revealed that most genetic risk factors for neurodegenerative diseases affect protein clearance pathways rather than directly causing disease.
In this special UK DRI research webinar, Prof Sir John Hardy and Prof Valentina Escott-Price present evidence for how this insight could resolve several key questions in the field:
- Why do we often see multiple pathologies in ageing brains?
- Why can the same genetic variants lead to different pathologies?
- Why does disease penetrance vary?
- Why are these conditions so age-dependent?
Their framework suggests that failing protein clearance systems may provide a unifying mechanism for understanding neurodegeneration, with important implications for therapeutic development.
Article reference:
Hardy, J., Escott-Price, V. The genetics of neurodegenerative diseases is the genetics of age-related damage clearance failure. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-02911-7
To note:
- The webinar will be chaired by UK DRI Emerging Leader Dr Natalie Connor-Robson.
- We'd like to thank the Connor-Robson Lab for providing the background graphics to the webinar showing amyloid beta protein phagocytosed by iPSC-derived microglia.
- The webinar is open to all internationally but the content and discussion will be aimed at a researcher audience.
Prof Sir John Hardy
Group Leader, UK DRI at UCL
A world-leading neurogeneticist in the field of neurodegenerative diseases, receiving numerous accolades that include the Breakthrough Prize in Life Sciences, the Brain Prize, election as a Fellow of the Royal Society and, in 2022, a knighthood for his contributions to science and health. In 1991, Hardy's team uncovered the first mutation directly implicated in Alzheimer's disease leading to the formulation of the highly influential 'amyloid-cascade' hypothesis.
Prof Valentina Escott-Price
Group Leader, UK DRI at Cardiff
Valentina's academic career began with a strong foundation in mathematics from St. Petersburg University in Russia, followed by a PhD in Statistics from Cardiff University. As a main member of the international Alzheimer's disease consortia, she played a crucial role in identifying new genetic loci linked to Alzheimer's. Her extensive multidisciplinary expertise spans genetic data analysis in dementias including Parkinson's disease, Vascular dementia, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, and dementia-related phenotypes. Her work focuses on accurately identifying individuals at high risk of disease, utilising polygenic risk scores, biomarkers and environmental risk factors.
Read more about the Escott-Price Lab
(Chair) Dr Natalie Connor-Robson
Emerging Leader, UK DRI at Cardiff
Natalie received her BSc in Biomedical Sciences from Cardiff University before completing her PhD on the role of the synuclein family in health and disease. In 2014, Dr Connor-Robson joined the Parkinson’s Disease Centre at the University of Oxford as a Career Development Fellow. During this time, she worked on understanding the earliest cellular pathogenic events to occur in Parkinson’s using both rodent models and iPSC-derived dopaminergic neurons. Her work highlighted the extensive roles of LRRK2 mutations in the endocytic and autophagic pathways as well as examining the role of GBA in Parkinson’s. In 2021, Natalie was awarded an ARUK Research Fellowship and joined the UKDRI as an Emerging Leader and in 2024 received an ARUK Senior Research Fellowship.