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A new blood test for early detection of Alzheimer’s disease

A dedicated analytical platform for measuring different populations of circulating amyloid β (Aβ) proteins – exosome-bound vs. unbound – directly from blood.

Alzheimer’s is the most common cause of dementia that causes problems with memory, thinking, and behavior. The disease accounts for 60% to 80% of the dementia cases.

Blood-based tests have the benefit of being safe, affordable, and easy to administer. In any case, one main challenge for scientists is that blood has low concentrations of AD molecules, and not all of particles atoms are disease-reflective, making detection and analysis troublesome.

This year has seen the development of a few types of blood tests that could potentially diagnose Alzheimer’s before symptoms appear. Now, scientists at the National University of Singapore have added one more new test to the list by developing a system APEX (Amplified Plasmonic EXosome).

Scientists invented the system to pick up an early-stage molecular marker of Alzheimer’s- the aggregated amyloid beta (Aβ). It is extremely sensitive and offers results with precision as compared to brain positron emission tomography (PET) imaging. What’s more, it could test 60 samples altogether and provide outcomes within an 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. The invention is the significant step forward by providing a solution to effectively ‘capture’ and measure the most meaningful AD molecules in blood samples and amplify them for analysis.

Assistant Professor Shao Huilin from the NUS Institute for Health Innovation & Technology (NUS iHealthtech) said, “There is currently a 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 potent and objective companion diagnostic system to complement existing clinical and neuropsychological tests for early detection and better management of AD.”

The APEX system could open doors to more effective detection of Alzheimer's disease
The APEX system could open doors to more effective detection of Alzheimer’s disease

“As blood tests are relatively easy to administer, APEX can also be 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.”

The disease is widely believed to be driven by the production and deposition of the β-amyloid peptide (Aβ). 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 analyze the earliest aggregated forms of Aβ proteins in blood samples, to enable detection of AD even before clinical symptoms appear and to classify the disease stages accurately.

Ms. Carine Lim, a doctoral student from NUS iHealthtech, said, “Traditional technologies measure all Aβ molecules found in the blood, regardless of their aggregation states, and thus show a 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.”

“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 analyze one blood sample.”

“Within each APEX sensor, there are millions of nanoholes to enable unique interactions with the aggregated Aβ. The APEX sensor recognizes the abnormal Aβ aggregates directly from a minimal amount of blood, induces, and amplifies a color change in the associated light signal.”

For the testing of the system, scientists conducted a clinical study, where they involved 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.

Asst Prof Shao reported, “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. This is the only blood test that shows such comparable results with PET imaging, the current gold standard for AD diagnosis.”

The team recently published its research findings in the prestigious scientific journal Nature Communications.

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