Researchers develop new blood test for faster, cheaper and more accurate detection of Alzheimer's

[Mista]

Doctors may one day be able to diagnose Alzheimer's disease (AD), the most common cause of severe dementia, and monitor a patient's response to treatment by doing a simple blood test. This is made possible using the APEX (Amplified Plasmonic EXosome) system invented by researchers from the National University of Singapore (NUS).


Designed to pick up an early-stage molecular marker of AD, the aggregated amyloid beta (Aβ), the APEX system could potentially diagnose AD even before clinical symptoms appear.

This novel technology is highly sensitive and provides an accurate diagnosis—comparable to brain PET imaging, the current gold standard for AD diagnosis—at about S$30 per test, which is less than one percent of the cost of PET imaging. The current design could test 60 samples simultaneously and results are available in less than one hour. As the APEX system uses native blood plasma without additional sample processing, it conducts direct measurement and is very simple to use in clinical settings.

Led by Assistant Professor Shao Huilin from the NUS Institute for Health Innovation & Technology (NUS iHealthtech), the 12-member research team spent two years developing APEX. The team recently published its research findings in prestigious scientific journal Nature Communications. The study was featured as an Editors' Choice by the journal.

Early detection and monitoring of AD

Dementia is the public health crisis of the 21st century. In 2018, dementia has affected 50 million people worldwide, and the number is expected to rise to 82 million by 2030 and 152 million by 2050. Every year, over 9.9 million new cases of dementia are diagnosed worldwide.

AD is the most common cause of dementia. Due to the complex and progressive nature of AD, early detection and intervention can improve the success of disease modifying therapies. Unfortunately, current AD diagnosis and monitoring—using clinical evaluation and neuropsychological assessments—are subjective and the disease tends to be detected only at a late stage. Other alternatives such as PET imaging and cerebrospinal fluid test are either too expensive for wide clinical adoption or require invasive lumbar punctures.

Blood-based tests, on the other hand, have the advantage of being safe, affordable and easy to administer. However, one key challenge for scientists is that blood has very low concentrations of AD molecules, and not all of these molecules are disease-reflective, making detection and diagnosis very difficult.


The invention by the NUS team is therefore a big step forward by providing a solution to effectively 'capture' and measure the most meaningful AD molecules in blood samples and amplify them for analysis.

Asst Prof Shao said, "There is currently no good blood-based method to effectively screen and monitor AD. New tests that are under investigation have either poor accuracy or low sensitivity. The APEX technology addresses both of these limitations and is therefore a very powerful and objective companion diagnostic system to complement existing clinical and neuropsychological tests for early detection and better management of AD."

"As blood tests are relatively easy to administer, APEX can be also used to monitor a patient's response to treatment. Furthermore, this technology can be easily scaled up for large cohort clinical validations and drug evaluation," she added.

Innovative APEX technology

A key characteristic of AD is the buildup of amyloid beta (Aβ) proteins in the brain. These Aβ proteins clump up as aggregates and kill brain cells. Aβ proteins are also released into, and circulate through, the bloodstream. The APEX system is uniquely designed to detect and analyse the earliest aggregated forms of Aβ proteins in blood samples, to enable detection of AD even before clinical symptoms appear and to accurately classify the disease stages.

"Traditional technologies measure all Aβ molecules found in the blood, regardless of their aggregation states, and thus show poor correlation to brain pathology. Our study found that the aggregated form of the protein could accurately reveal brain changes and reflect AD disease stages," said Ms Carine Lim, a doctoral student from NUS iHealthtech and NUS Department of Biomedical Engineering, and co-first author of the study.

The APEX technology is size-matched to distinguish this group of reflective Aβ proteins directly from blood samples. Each APEX chip is 3 cm by 3 cm—about a quarter the size of a credit card, and contains 60 neatly-arranged sensors, each to analyse one blood sample.

"Within each APEX sensor, there are millions of nanoholes to enable unique interactions with the aggregated Aβ. The APEX sensor recognises the abnormal Aβ aggregates directly from a very small amount of blood, induces and amplifies a colour change in the associated light signal," said Mr Zhang Yan, a doctoral student from NUS iHealthtech and NUS Department of Biomedical Engineering, and co-first author of the study.

Superior results from clinical study

To determine the performance of the APEX system, Asst Prof Shao and her team conducted a clinical study involving 84 individuals, including patients who have been diagnosed with AD or mild cognitive impairment (MCI), as well as a control group comprising healthy individuals and patients diagnosed with vascular dementia or neurovascular compromises. PET imaging and blood sampling were conducted on all participants.

"The results of the APEX tests correlate extremely well with PET imaging results. The clinical study shows that the APEX system can accurately identify patients with AD and those with MCI; it also differentiates them from healthy individuals and patients suffering from other neurodegenerative diseases. In fact, this is the only blood test that shows such comparable results with PET imaging, the current gold standard for AD diagnosis," Asst Prof Shao explained.

Next steps

Asst Prof Shao and her team are currently in discussions with industry partners to commercialise this technology. The device is expected to reach market within the next 5 years.

In the next phase of research, the team hopes to employ the technology in areas of AD disease management as well as for evaluation of AD therapeutics under development.

https://medicalxpress.com/news/2019-06-blood-faster-cheaper-accurate-alzheimer.html

 

[Mista]

NUS scientists develop world’s first blood test to accurately detect Alzheimer’s disease

SINGAPORE — A team of researchers at the National University of Singapore (NUS) has developed a new blood test to detect Alzheimer’s disease that it says is the fastest and most accurate in the world.

The Amplified Plasmonic Exosome (Apex) system is able to detect mild cognitive impairment and Alzheimer’s disease, which leads to severe dementia, and can provide results within an hour, after analysing certain proteins in blood samples.

Currently, there are three ways to diagnose dementia: A neuropsychological test, spinal fluid sampling and brain Positron Emission Tomography (PET) imaging.

The most common method is the neuropsychological test, while the PET scan is considered the most accurate test on the market now.

The brain PET imaging uses a special dye which contains radioactive tracers, that patients would have to either inhale or receive it through an injection. The patient would then have to wait an hour for the tracer to be absorbed by the body.

The areas of the brain containing disease would then appear as coloured spots on the PET scan.

Assistant professor Shao Huilin from NUS Institute for Health Innovation & Technology (NUS iHealthtech), who led the study, said: “The clinical study shows that the Apex system can accurately identify patients with Alzheimer’s and those with mild cognitive impairment (MCI). It also differentiates them from healthy individuals and patients suffering from other neurodegenerative diseases.”

She added that the blood test shows “comparable results with PET imaging, the current gold standard for Alzheimer’s diagnosis”.

The blood test is expected to be in use in hospitals and general practitioner clinics within the next five years, Prof Shao said, adding that it will priced at around S$30.

The current design can test 60 samples simultaneously, with the results being available in less than one hour.

Last year alone, dementia affected 50 million patients worldwide and the number is expected to increase to 82 million by 2030 and 152 million by 2050.

Every year, there are more than 9.9 million new cases of dementia diagnosed worldwide.

A study conducted by Singapore's Institute of Mental Health in 2015 estimated that one in 10 people in Singapore over the age of 60 had dementia. It also projected that there would be more than 100,000 dementia patients here in a few years’ time.

Prof Shao hopes that this new blood test will be able to help stem the tide.

“With this new blood test to enable early detection for Alzheimer’s disease, we think that it can offer many new opportunities for intervention and management. For example, by encouraging lifestyle changes, more active participation in cognitive as well as physical activities, we can regulate the progression of the disease.”

The early detection of Alzheimer’s can also help facilitate the discovery and development of new drugs, she added.

Out of the 84 patients involved in the clinical study, all 68 who have dementia or neurovascular compromises were diagnosed by the blood test.

Prof Shao noted that for now, there is no good blood-based method to effectively screen and monitor Alzheimer’s, making the NUS test a world’s first.

“New tests that are under investigation have either poor accuracy or low sensitivity. The Apex technology addresses both of these limitations and is therefore a very powerful and objective companion diagnostic system to complement existing clinical and neuropsychological tests for early detection and better management of the disease,” she said.

She added that the convenience of blood tests will also be able to allow doctors to monitor a patient’s response to treatment.

“This technology can be easily scaled up for large-cohort clinical validations and drug evaluation.”

https://www.todayonline.com/singapo...ood-test-accurately-detect-alzheimers-disease

 

[Dubious]

Awesome stuff!

 

[waz]

Doctors may one day be able to diagnose Alzheimer's disease (AD), the most common cause of severe dementia, and monitor a patient's response to treatment by doing a simple blood test. This is made possible using the APEX (Amplified Plasmonic EXosome) system invented by researchers from the National University of Singapore (NUS).


Designed to pick up an early-stage molecular marker of AD, the aggregated amyloid beta (Aβ), the APEX system could potentially diagnose AD even before clinical symptoms appear.

This novel technology is highly sensitive and provides an accurate diagnosis—comparable to brain PET imaging, the current gold standard for AD diagnosis—at about S$30 per test, which is less than one percent of the cost of PET imaging. The current design could test 60 samples simultaneously and results are available in less than one hour. As the APEX system uses native blood plasma without additional sample processing, it conducts direct measurement and is very simple to use in clinical settings.

Led by Assistant Professor Shao Huilin from the NUS Institute for Health Innovation & Technology (NUS iHealthtech), the 12-member research team spent two years developing APEX. The team recently published its research findings in prestigious scientific journal Nature Communications. The study was featured as an Editors' Choice by the journal.

Early detection and monitoring of AD

Dementia is the public health crisis of the 21st century. In 2018, dementia has affected 50 million people worldwide, and the number is expected to rise to 82 million by 2030 and 152 million by 2050. Every year, over 9.9 million new cases of dementia are diagnosed worldwide.

AD is the most common cause of dementia. Due to the complex and progressive nature of AD, early detection and intervention can improve the success of disease modifying therapies. Unfortunately, current AD diagnosis and monitoring—using clinical evaluation and neuropsychological assessments—are subjective and the disease tends to be detected only at a late stage. Other alternatives such as PET imaging and cerebrospinal fluid test are either too expensive for wide clinical adoption or require invasive lumbar punctures.

Blood-based tests, on the other hand, have the advantage of being safe, affordable and easy to administer. However, one key challenge for scientists is that blood has very low concentrations of AD molecules, and not all of these molecules are disease-reflective, making detection and diagnosis very difficult.


The invention by the NUS team is therefore a big step forward by providing a solution to effectively 'capture' and measure the most meaningful AD molecules in blood samples and amplify them for analysis.

Asst Prof Shao said, "There is currently no good blood-based method to effectively screen and monitor AD. New tests that are under investigation have either poor accuracy or low sensitivity. The APEX technology addresses both of these limitations and is therefore a very powerful and objective companion diagnostic system to complement existing clinical and neuropsychological tests for early detection and better management of AD."

"As blood tests are relatively easy to administer, APEX can be also used to monitor a patient's response to treatment. Furthermore, this technology can be easily scaled up for large cohort clinical validations and drug evaluation," she added.

Innovative APEX technology

A key characteristic of AD is the buildup of amyloid beta (Aβ) proteins in the brain. These Aβ proteins clump up as aggregates and kill brain cells. Aβ proteins are also released into, and circulate through, the bloodstream. The APEX system is uniquely designed to detect and analyse the earliest aggregated forms of Aβ proteins in blood samples, to enable detection of AD even before clinical symptoms appear and to accurately classify the disease stages.

"Traditional technologies measure all Aβ molecules found in the blood, regardless of their aggregation states, and thus show poor correlation to brain pathology. Our study found that the aggregated form of the protein could accurately reveal brain changes and reflect AD disease stages," said Ms Carine Lim, a doctoral student from NUS iHealthtech and NUS Department of Biomedical Engineering, and co-first author of the study.

The APEX technology is size-matched to distinguish this group of reflective Aβ proteins directly from blood samples. Each APEX chip is 3 cm by 3 cm—about a quarter the size of a credit card, and contains 60 neatly-arranged sensors, each to analyse one blood sample.

"Within each APEX sensor, there are millions of nanoholes to enable unique interactions with the aggregated Aβ. The APEX sensor recognises the abnormal Aβ aggregates directly from a very small amount of blood, induces and amplifies a colour change in the associated light signal," said Mr Zhang Yan, a doctoral student from NUS iHealthtech and NUS Department of Biomedical Engineering, and co-first author of the study.

Superior results from clinical study

To determine the performance of the APEX system, Asst Prof Shao and her team conducted a clinical study involving 84 individuals, including patients who have been diagnosed with AD or mild cognitive impairment (MCI), as well as a control group comprising healthy individuals and patients diagnosed with vascular dementia or neurovascular compromises. PET imaging and blood sampling were conducted on all participants.

"The results of the APEX tests correlate extremely well with PET imaging results. The clinical study shows that the APEX system can accurately identify patients with AD and those with MCI; it also differentiates them from healthy individuals and patients suffering from other neurodegenerative diseases. In fact, this is the only blood test that shows such comparable results with PET imaging, the current gold standard for AD diagnosis," Asst Prof Shao explained.

Next steps

Asst Prof Shao and her team are currently in discussions with industry partners to commercialise this technology. The device is expected to reach market within the next 5 years.

In the next phase of research, the team hopes to employ the technology in areas of AD disease management as well as for evaluation of AD therapeutics under development.

https://medicalxpress.com/news/2019-06-blood-faster-cheaper-accurate-alzheimer.html

Well done to Singapore! Excellence in innovation. This is what makes a world leading economy. I'm proud that my relatives helped build this country.