Proteins in human body reveal warning signs for Alzheimer’s and Parkinson’s
Analysis of large biological dataset uncovers clues that could help detect and combat neurodegenerative conditions
An international probe into the human body’s proteins has revealed new clues about ageing and how to track and treat destructive neurological diseases such as Alzheimer’s and Parkinson’s.
Research on the largest-ever protein library is helping bring humanity “closer than ever to the day when a diagnosis of Alzheimer’s disease stops being a death sentence”, said billionaire philanthropist Bill Gates, who part-funded the work.
The findings published in several Nature Medicine papers on Tuesday are part of an escalating effort to combine big biological datasets with artificial intelligence-enhanced analysis to find early predictors that can help detect and combat notoriously hard-to-treat conditions.
Researchers used the data to identify a signature protein — or biomarker — associated with carriers of a genetic variant known to raise the risk of Alzheimer’s. They also examined how levels of proteins that correlate with cognitive function changed with age, and uncovered patterns in protein level changes for various neurodegenerative conditions.
“The most immediately exciting part is that the patterns of protein abnormality that predict neurodegenerative diseases reveal new insights into the biology of how these conditions develop,” said Charles Marshall, a professor of clinical neurology at Queen Mary University of London.
“This paves the way for drug discovery work that could ultimately lead to new treatments,” he said.
The work is part of an initiative set up in 2023 known as the Global Neurodegeneration Proteomics Consortium (GNPC). It brings together research institutions with the backing of Johnson & Johnson and Gates Ventures, the private office of the Microsoft co-founder.
Simon Lovestone, global head of discovery and translational research at the pharmaceuticals company Johnson & Johnson, said that after decades of gradual incremental progress, the field of neurodegeneration was rapidly accelerating.
“The scale and depth of the dataset, combined with harmonised clinical data, make it an extraordinary resource with the potential to transform how we study, detect and treat neurodegenerative diseases,” he said.
The consortium has built a dataset of about 250mn unique protein measurements and 35,000 biosamples from 23 participant groups in the US and Europe, plus other anonymised clinical information. It is being made available to researchers and other interested parties for free online.
Neurodegenerative diseases are estimated to affect over 50mn people worldwide and the number is projected to double by 2050, driven in part by population ageing. Cases of Alzheimer’s, the most common cause of dementia, and Parkinson’s, which affects movement and other faculties, have increased particularly rapidly compared with other conditions.
The papers highlighted the importance of using large datasets when investigating neurodegenerative diseases, said Amanda Heslegrave, principal research fellow at the UK Dementia Research Institute Biomarker Factory at UCL.
The work exploring the “overlapping biology” between Alzheimer’s and Parkinson’s could boost emerging efforts to jointly tackle the conditions, said Simon Stott, research director for Cure Parkinson’s. The charity is partnering with its counterpart Alzheimer’s Research UK to assess drugs that could be mutually beneficial.
“Biomarkers are crucial for improving not only our understanding of the underlying biology of these diseases, but also for our clinical trials that seek to correct them,” Stott said.
“[They] allow us to monitor patients during clinical trials and determine if the experimental drug being tested is having its desired effect.”