New research offers fresh hope for diagnosing Alzheimer's via a blood test, potentially years before symptoms emerge.
The memory-robbing disease has no set test, with specialists assessing suspected patients via memory analyses, mental-agility evaluations and brain scans.
The concept of an Alzheimer's blood test is not new, with past studies suggesting biomarkers circulate in a patient's blood before they show signs of the disease.
Cutting-edge technology has now enabled scientists from the University of Manchester to uncover previously-unseen blood biomarkers in mice with the memory-robbing condition.
Alzheimer's is considered incurable, however, treatments can temporarily ease symptoms, with these being more effective when administered early in the disease's onset.
Alzheimer's is the most common form of dementia, an umbrella term for syndromes associated with an ongoing loss of brain function.
More than 850,000 people had dementia in the UK in 2019, with Alzheimer's affecting 50% to 75% of these patients. In the US, over 6 million people have Alzheimer's.
Blood biomarkers are believed to be present in Alzheimer's patients, however, their minute level makes them difficult to detect.
The Manchester scientists therefore created a specific nanotechnology – "the study and application of extremely small things" – that allowed them to extract blood signals from mice with the disease.
These signals could then be magnified, enabling the team to look for signs of Alzheimer's.
"Hidden information in blood is likely to echo the complex cascade of events occurring in the brain of Alzheimer's disease patients," said lead author Dr Marilena Hadjidemetriou.
"We wanted to engineer a nanotechnology blood-mining platform in order to uncover this information and identify early signs of Alzheimer’s disease at the pre-disease state, before the onset of amyloid plaque formation in the brain.’"
Amyloid is a normally-occurring protein, however, it accumulates in Alzheimer's patients. This causes plaques to form around brain cells.
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The Manchester team's nanotechnology model enhanced the sensitivity of mass spectrometry, an analytical tool that uncovers the patterns of proteins in blood.
Liposomes, nano-sized spheres, were then used to "fish out" disease-specific proteins.
When injected into mice with Alzheimer's, the nanoparticles accumulated hundreds of neurodegeneration-associated proteins onto their surface, the scientists reported in the journal ACS Nano.
The nanoparticles were then retrieved and the molecular signatures on their surface analysed.
"This study was rather like a fishing expedition: we didn't know what was beneath the surface of the ocean," said co-author Professor Kostas Kostarelos.
"The nano-tool we developed allowed us to see deeper into the blood proteome, identifying proteins of interest that are directly associated with neurodegeneration processes in the brain, among thousands of other blood-circulating molecules.
"We hope these early warning signs of Alzheimer's disease could one day be developed into a blood test and we are actively seeking validation of these signatures in human blood."
By tracking protein levels at different stages of the mice's Alzheimer's, the team identified complex disease-monitoring patterns.
"We were extremely interested in the fluctuation of protein levels at different disease stages, from the pre-diseased state, to the intermediate state between amyloidopathy and cognitive symptoms, and finally symptomatic disease," said co-author Dr Catherine Lawrence.
Amyloidopathy describes the presence of amyloid plaques in the brain.
"These findings indicate single-time point blood biomarker discovery studies provide only a snapshot of the blood proteome [the complete set of proteins expressed by an organism]," said Dr Lawrence.
"This could explain previously reported inconsistent results and the lack of clinically-used blood-based biomarkers for Alzheimer's disease."
Co-author Professor Nigel Hooper added: "The technology developed opens up new possibilities for the development of novel multi-analyte blood tests to predict the onset and development of a wide range of neurodegenerative disorders."
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