Alzheimer's & Dementia

Simple test predicts Alzheimer's risk, 20 years before symptoms show

Simple test predicts Alzheimer's risk, 20 years before symptoms show
Researcher Shankar Dutt with a new diagnostic tool that can isolate proteins from other biomolecules in the blood to search for signs of early neurodegeneration
Researcher Shankar Dutt with a new diagnostic tool that can isolate proteins from other biomolecules in the blood to search for signs of early neurodegeneration
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Researcher Shankar Dutt with a new diagnostic tool that can isolate proteins from other biomolecules in the blood to search for signs of early neurodegeneration
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Researcher Shankar Dutt with a new diagnostic tool that can isolate proteins from other biomolecules in the blood to search for signs of early neurodegeneration
Professor Patrick Kluth says the new technology could also detect one’s risk of developing Parkinson’s disease or multiple sclerosis
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Professor Patrick Kluth says the new technology could also detect one’s risk of developing Parkinson’s disease or multiple sclerosis
Sketch of protein translocation through a SiNx nanopore membrane. The proteins in a buffered electrolyte solution are placed in the cis and trans channels depending on the charge and polarity of the applied voltage. Silver-silver chloride electrodes are used to apply a bias across the membrane. b) Photographs of the portable amplifiers used for data acquisition: Elements 10 MHz and 100 kHz nanopore readers providing a sampling rate of 40 Msps and 200 ksps, respectively. c) Different proteins used in the present study. Protein structures were obtained from the Protein Data Bank website of the Research Collaboratory for Structural Bioinformatics. d,e) Representative ionic current-time traces of different proteins under bias dc voltage ranging from 300 to 600 mV recorded at sampling rates of 200 ksps and 40 Msps, respectively. f,g) Event shape transformation showing the loss of detail during low-pass filtering: comparison of the unfiltered signal and signals filtered at 35 kHz and 10 kHz frequencies (acquisition at 200 ksps) (f) and 1 MHz, 500 kHz, 100 kHz, and 35 kHz frequencies (acquisition at 40 Msps) (g). The measurements of Hb, HSA, BSA, and Con A proteins were conducted in electrolyte solutions with pH of 7.94, 7.92, 8.02, and 8.02 respectively.
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Sketch of protein translocation through a SiNx nanopore membrane. The proteins in a buffered electrolyte solution are placed in the cis and trans channels depending on the charge and polarity of the applied voltage. Silver-silver chloride electrodes are used to apply a bias across the membrane. b) Photographs of the portable amplifiers used for data acquisition: Elements 10 MHz and 100 kHz nanopore readers providing a sampling rate of 40 Msps and 200 ksps, respectively. c) Different proteins used in the present study. Protein structures were obtained from the Protein Data Bank website of the Research Collaboratory for Structural Bioinformatics. d,e) Representative ionic current-time traces of different proteins under bias dc voltage ranging from 300 to 600 mV recorded at sampling rates of 200 ksps and 40 Msps, respectively. f,g) Event shape transformation showing the loss of detail during low-pass filtering: comparison of the unfiltered signal and signals filtered at 35 kHz and 10 kHz frequencies (acquisition at 200 ksps) (f) and 1 MHz, 500 kHz, 100 kHz, and 35 kHz frequencies (acquisition at 40 Msps) (g). The measurements of Hb, HSA, BSA, and Con A proteins were conducted in electrolyte solutions with pH of 7.94, 7.92, 8.02, and 8.02 respectively.

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Australian National University (ANU) physicists have combined nanotechnology, artificial intelligence and molecular biology to design a novel method that looks for Alzheimer’s disease protein markers in blood. These markers are tell-tale signs of early neurodegeneration, and early detection is so far the best defense we have in order to effectively intervene in Alzheimer’s progression. While there’s no cure for the disease, a 20-year jump on symptoms first appearing has the potential to significantly change health outcomes.

While a large body of research is focused on developing targeted therapeutics for treating advanced Alzheimer's, there has also been a lot of progress made in the field of advanced diagnostics.

"Currently, Alzheimer's is mostly diagnosed based on evidence of mental deterioration, by which stage the disease has already seriously damaged the brain,” said co-author Professor Patrick Kluth, from the ANU Research School of Physics. “Early detection, which is vital for effective treatment, normally involves invasive and expensive hospital procedures such as a lumbar puncture, which can be physically and mentally taxing for patients."

The researchers developed an ultra-thin silicon chip covered in tiny, nanometer-sized holes, or solid-state nanopores. A small amount of blood is then placed on the chip, and through a process of translocation through the nanopores, complex mixes of proteins in the blood could be isolated. Then, the chip was inserted into a phone-sized device, where an artificial intelligence algorithm searched for protein signatures that matched with those associated with early onset Alzheimer’s disease.

And by classifying protein signals into clusters based on signal attributes, the researchers found the model returned both a significant and high degree of accuracy (specificity of 96.4%) in identifying combinations of the four machine-learned proteins. Since proteins contain distinct and individualized genetic blueprints, they can play a much larger role in diagnostic medicine, given the right technology.

"If that person can find out their risk level that far in advance, then it gives them plenty of time to start making positive lifestyle changes and adopt medication strategies that may help slow down the progression of the disease,” said co-author Shankar Dutt, a researcher at ANU.

Professor Patrick Kluth says the new technology could also detect one’s risk of developing Parkinson’s disease or multiple sclerosis
Professor Patrick Kluth says the new technology could also detect one’s risk of developing Parkinson’s disease or multiple sclerosis

While Alzheimer’s focused, the researchers point out the algorithm used can be trained up to look for other diseases – and to test for them at the same time. Those include Parkinson’s disease, multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).

“Blood is a complex fluid that contains more than 10,000 different biomolecules,” Dutt said. “By employing advanced filtration techniques and harnessing our nanopore platform, combined with our intelligent machine learning algorithms, we may be able to identify even the most elusive proteins.”

The team hopes this screening technique will be available within the next five years, allowing patients to get results “in near real time,” added Kluth.

"The quick and simple test could be done by GPs and other clinicians, which would eliminate the need for a hospital visit and prove especially convenient for people living in regional and remote areas,” he said.

The research is published in the journal Small Methods.

Source: Australian National University

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1 comment
1 comment
Ric
Five years makes what could be a 20 year advance notice into a fifteen year advance notice and a five year notice into no notice at all. I suggest they fast track this test for what will undoubtedly be one of the most tragic epidemics we are surely facing as the global population ages.