Alzheimer’s disease could soon be diagnosed and monitored with a low-cost blood test developed by researchers from the National University of Singapore.
The advance has been possible with a so-called APEX (Amplified Plasmonic EXosome) system that detects aggregated amyloid beta (Aβ), an early-stage molecular marker of AD.
According to NUS, the chip technology is comparable to brain PET imaging, the current gold standard for AD diagnosis, but costs about S$30 per test, or less than one per cent of the cost of PET imaging.
The current design could test 60 samples simultaneously and results are available in under an hour. As the APEX system uses native blood plasma without additional sample processing, it conducts direct measurement and is easy to use in clinical settings.
Led by Assistant Professor Shao Huilin from the NUS Institute for Health Innovation & Technology (NUS iHealthtech), the research team spent two years developing APEX and recently published its research findings in Nature Communications.
Early detection and intervention can improve the success of treatments but current AD diagnosis and monitoring – using clinical evaluation and neuropsychological assessments – are subjective and the disease tends to be detected at a late stage. Other alternatives such as PET imaging and cerebrospinal fluid test are expensive or require invasive lumbar punctures.
Blood tests are safe, affordable and easy to administer but a 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 difficult.
In a statement, 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.”
Aβ proteins clump up as aggregates and kill brain cells. Aβ proteins are also released into, and circulate through, the bloodstream. The APEX system detects and analyses 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 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 said to be size-matched to distinguish this group of reflective Aβ proteins directly from blood samples. Each APEX chip is 3cm x 3cm and contains 60 sensors to analyse one blood sample each.
“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 Zhang Yan, a doctoral student from NUS iHealthtech and NUS Department of Biomedical Engineering, and co-first author of the study.
Asst Prof Shao and her team conducted a clinical study involving 84 individuals, including patients diagnosed with AD or mild cognitive impairment (MCI), plus a control group of 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.
Asst Prof Shao and her team are currently in discussions with industry partners to commercialise the technology, which is expected to reach market within the next five years.