AsianScientist (Jul. 12, 2019) – Doctors may one day be able to diagnose Alzheimer’s disease (AD) with a simple blood test. These findings, published in Nature Communications, were by researchers from the National University of Singapore (NUS).
Dementia is the public health crisis of the 21st century. In 2018, dementia 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 tests 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.
In the present study, a team of researchers led by Assistant Professor Shao Huilin developed a sensor that can pick up an early-stage molecular marker of AD, the aggregated amyloid beta (Aβ). Called Amplified Plasmonic EXosome (APEX), the system could potentially diagnose AD even before clinical symptoms appear, the researchers said.
“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 study co-author, Ms. Carine Lim.
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 sensors.
“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 very small amount of blood, induces and amplifies a colour change in the associated light signal,” said study co-first author Mr. Zhang Yan.
To determine the performance of the APEX system, Shao and her team conducted a clinical study involving 84 individuals, including patients who have been diagnosed with AD or mild cognitive impairment, as well as a control group comprising healthy individuals and patients diagnosed with vascular dementia or neurovascular compromises.
“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,” Shao explained.
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 five years. In the next phase of research, the team hopes to use the technology for disease management, as well as to evaluate therapeutics under development.
The article can be found at: Lim et al. (2019) Subtyping of Circulating Exosome-bound Amyloid Β Reflects Brain Plaque Deposition.
Source: National University of Singapore.
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