Novel Ultrasensitive Detection Technologies for the Identification of Early and Minimally Invasive Alzheimer's Disease Blood Biomarkers

Background: Single molecule array (SIMOA) and other ultrasensitive detection technologies have allowed the determination of blood-based biomarkers of Alzheimer's disease (AD) for diagnosis and monitoring, thereby opening up a promising field of research. Objective: To review the published bibliography on plasma biomarkers in AD using new ultrasensitive techniques. Methods: A systematic review of the PubMed database was carried out to identify reports on the use of blood-based ultrasensitive technology to identify biomarkers for AD. Results: Based on this search, 86 works were included and classified according to the biomarker determined. First, plasma amyloid-beta showed satisfactory accuracy as an AD biomarker in patients with a high risk of developing dementia. Second, plasma t-Tau displayed good sensitivity in detecting different neurodegenerative diseases. Third, plasma p-Tau was highly specific for AD. Fourth, plasma NfL was highly sensitive for distinguishing between patients with neurodegenerative diseases and healthy controls. In general, the simultaneous determination of several biomarkers facilitated greater accuracy in diagnosing AD (A beta(42)/A beta(40), p-Tau181/217). Conclusion: The recent development of ultrasensitive technology allows the determination of blood-based biomarkers with high sensitivity, thus facilitating the early detection of AD through the analysis of easily obtained biological samples. In short, as a result of this knowledge, pre-symptomatic and early AD diagnosis may be possible, and the recruitment process for future clinical trials could be more precise. However, further studies are necessary to standardize levels of blood-based biomarkers in the general population and thus achieve reproducible results among different laboratories.