For the first time, researchers have successfully visualized and quantified small protein clusters in the human brain that may signal the onset of Parkinson’s disease.
These clusters, known as alpha-synuclein oligomers, have long been implicated in some of the fastest-expanding neurological disorders worldwide but had never been observed in brain tissue until now.
To identify these elusive proteins, the research team utilized a novel imaging method called Advanced Sensing of Parkinson’s Disease (ASA-PD) aggregates, which renders these nanometer-scale (one billionth of a meter) oligomers visible.
For decades, clinicians could confirm a diagnosis of Parkinson’s disease only by detecting larger deposits of proteins that build up in neurons. However, many researchers believe the disease actually initiates with these smaller oligomers.
“You can think of Lewy bodies as a sort of morbid gravestone,” stated Professor Stephen Lee from Cambridge’s Yusuf Hameed Department of Chemistry, who co-led the study. BBC Science Focus. “They indicate where the disease resides and its progression.”
To investigate the earlier phases of the disease, the team compared post-mortem brain samples from individuals with Parkinson’s disease to those from healthy individuals. Oligomers were present in both cohorts, surprising scientists, but were more abundant and vibrant in the brains of Parkinson’s patients.
“This marks the first occasion we’ve directly observed oligomers in human brain tissue at this scale, akin to spotting stars in daylight,” commented Dr. Rebecca Andrews, Co-First Author and former postdoctoral researcher in Lee’s lab.
The researchers also discovered subtle variations in the distribution of oligomers, which could signify the earliest stages of the disease prior to the onset of symptoms.
Lee emphasized that while this study is a significant advancement, it should not be misconstrued as a means to directly find treatments. “We’re not at that stage,” he noted. “This research actually allows us to engage with the very early stages of the disease. From a therapeutic standpoint, it lays the groundwork for future developments.”
Currently, over 10 million people globally suffer from Parkinson’s disease, which lacks a treatment that addresses the underlying condition. Existing medications can manage symptoms like tremors, but none target the disease’s root cause or halt its progression.
A collaborative team from the University of Cambridge, the University of London, the Francis Crick Institute, and Polytechnique Montreal aims to utilize these findings to enhance methods for monitoring the efficacy of diagnostic tests and experimental treatments.
This imaging technique is also applicable beyond just Parkinson’s disease. “This approach provides more than just a snapshot,” said Professor Lucian Weiss from Polytechnique Montréal, who co-led the study. “It maps protein changes throughout the brain and similar techniques can be applied to other neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases.”
“Oligomers were once like needles in a haystack, and now that we know their precise locations, it enables us to target specific cell types in designated areas of the brain.”
The findings of this study have been published in Nature Biomedical Engineering.
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Source: www.sciencefocus.com
