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Blood Test for Detecting Pre-symptomatic Alzheimer's Disease is Refined

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A research team led by YoungSoo Kim at Yonsei University have developed a method to detect the amyloid-beta (Aβ) peptide in human blood. They hope that their research will have implications in diagnosing and understanding the progression of Alzheimer's disease (AD).

Alzheimer's disease

The exact underlying cause of AD in patients is a scientific mystery that remains to be solved. Whilst there are familial forms that shed light on potential genetic implications, for most patients, AD occurs sporadically.

What we do know is that there are consistent brain changes occurring across AD patients, including the accumulation of Aβ peptides that form plaques outside of neurons, and tangles of proteins called tau inside neurons.

A difficult diagnosis

Kim and colleagues look to utilize these pathological hallmarks of AD to create a much-needed novel diagnostic tool – a blood test. Current approaches to diagnosing AD rely heavily on self-reporting measures or observant relatives or friends noticing a difference in an individual's behavior. Considering that symptoms of the disease aren't overly distinguishable from the symptoms of old age, it is not uncommon for AD to progress significantly before a diagnosis is made.

As the Aβ peptide can travel from the brain to the blood, it presents as a potential biomarker for AD that can be measured systemically in a blood sample. "Aβ abnormality precedes aforementioned AD’s pathological events and blood tests are common methods to detect/suspect at-risk patients," says Kim. 

A non-invasive blood test for Alzheimer's disease

However, debate has arisen as to whether Aβ levels in the blood accurately reflect the progression of AD the brain, putting the brakes on this area of research.

In their latest study, published in Science Advances, Kim and colleagues have utilized a novel method in which a small molecule, EPPS, is used to break up Aβ aggregates in the blood into smaller molecules that can then be detected in small concentrations by a sensor. Their study involved samples from a control group and blood samples from individuals previously diagnosed with AD using conventional methods.

"We used two technologies in this study: 1) the comparing levels of Aβ by self-standard (CLASS) method for dissociating oligomeric plasma Aβ and 2) interdigitated microelectrode (IME) sensor system to detect plasma Aβ in pico molar level changes," comments Kim.

The researchers found that using the CLASS method to analyze plasma that has been treated by EPPS allowed them to reliably distinguish between patients with AD from those in the control group. They also show that this technique can be reliably used as used as a qualitative approach for assessing AD progression. 

From the lab bench to the clinic

Kim emphasizes that the potential of this method has been realized, and that appropriate steps are being taken to ensure it can be delivered to the clinic as a non-invasive AD diagnostic tool. "Currently, we are working on larger scale clinical investigation. This technology is owned by our former affiliation, Korea Institute of Science and Technology, and it will be their decision to make this commercially available, but we believe this technology needs to be marketed as soon as possible."

Reference: Kim et al. 2019. Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system. Science Advances. DOI: 10.1126/sciadv.aav1388.