The nanotubes were able to measure microscopic concentrations of Alzheimer’s main protein biomarkers in blood plasma, and reportedly distinguished Alzheimer’s patients from healthy people with an average accuracy of 88.6%.
These results were detailed in the study, “Blood-based multiplexed diagnostic sensor helps to accurately detect Alzheimer’s disease,” published in Nature Communications.
Alzheimer’s is a neurodegenerative disease marked by the death of nerve cells, or neurons. Two of the main clinical findings associated with this neuronal death are the formation of amyloid plaques — aggregation of amyloid-beta into clumps— and tau tangles — abnormal aggregates of tau protein — inside the brain.
Four molecules serve as the main biomarkers for Alzheimer’s disease: amyloid-beta 42, amyloid-beta 40, total tau protein (t-tau) and phosphorylated tau protein (p-tau).
Amyloid-beta 42 and 40 are two isoforms (protein variants) of the amyloid-beta protein that have different lengths and whose levels are higher-than-usual in the context of Alzheimer’s disease. Phosphorylated tau protein is a toxic version of the tau protein that clumps together to form the tangles that eventually result in the death of nerve cells.
Because both Alzheimer’s disease and other forms of dementia are complex disorders that involve many biological factors, simultaneously detecting multiple biomarkers has a strong advantage.
The psychological and neuroimaging tests that are currently used to diagnose Alzheimer’s are expensive and can be inaccurate. This causes many Alzheimer’s patients to be diagnosed late, when treatments are less effective or not at all helpful.
Diagnosis before the onset of symptoms might significantly reduce the risk of developing Alzheimer’s though actions like lifestyle modifications, and some studies have shown that the levels of p-tau, t-tau, and beta-amyloid 42 start to change roughly 10 to 15 years before the onset of symptoms.
Researchers in South Korea tested their nanotubes on blood plasma samples taken from 20 Alzheimer’s patients older than 65 (mean age, 72.5 ) and from 20 healthy people serving as controls (mean age, 70.8).
Although the concentrations of Alzheimer’s biomarkers are lower in the blood than in the cerebrospinal fluid (CSF), there is a strong correlation between the levels of these biomarkers in blood plasma and disease-related changes in the brain.
A distinguishing feature of the nanotubes used in this study is that they were arrayed in dense sheets, in which all the nanotubes were aligned with each other, like pencils placed neatly side-by-side. Antibodies specific for each of the targeted biomarkers were fixed to the surface of these sheets, and used to trap the various biomarkers as they flowed over the sheet.
This tidy arrangement proved to be much more efficient and sensitive than other carbon nanotube sensors, which are arrayed in a more random configuration.
The nanotubes selectively identified these biomarkers with a selectivity of 90.0%, an average accuracy of 88.6%, and with up to 100 times higher sensitivity than conventional nanotube-based biosensors.
Importantly, the high sensitivity and specificity that the nanotubes showed for the Alzheimer’s-related biomarkers was not affected by the large numbers of unrelated molecules found in blood plasma samples.
Linking receptors for the four types of biomarkers to the carbon nanotube array enabled the array to selectively detect these molecules at extremely low concentrations. This heightened sensitivity contributed to the nanotubes’ ability to distinguish between Alzheimer’s patients and healthy controls at such a high accuracy.
“Simultaneous detection of multiple biomarkers is highly desirable because of the heterogeneity of dementia pathology and the complexity of AD [Alzheimer’s disease] pathogenesis,” the researchers wrote.
Although the researchers point out that more can be done to improve the sensitivity of their sensor, and that larger scale tests in patient groups are needed to confirm their findings and translate them into clinical use, their current results show a “high potential” for aligned carbon nanotube-based sensing platforms to aid in the early diagnosis of Alzheimer’s disease.
“This study was conducted on patients who are already confirmed with Alzheimer’s Disease. For further use in practical setting, it is necessary to test the patients with mild cognitive impairment,” Steve Park, a study researcher and professor of materials science and engineering at the Korea Advanced Institute of Science and Technology, said in a press release.
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