iMEP – sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer’s disease

In recent years, blood exosomes have emerged as promising indicators for diagnosing neurodegenerative conditions like Alzheimer’s disease (AD). However, the lack of highly sensitive technology has hindered their effective use in clinical settings. Addressing this challenge, a groundbreaking study has introduced the immunomagnetic exosomal polymerase chain reaction (iMEP) platform, revolutionizing the detection of core AD biomarkers in blood exosomes.

The iMEP platform utilizes DNA-conjugated antibodies to swiftly identify key biomarkers associated with AD, namely amyloid-β (Aβ1–40 and Aβ1–42) and phosphorylated tau (p-tau396,404 and p-tau181), within clinical blood exosomes. By employing toehold shift–mediated DNA affinity pulldown, this innovative method significantly reduces detection background, enabling the identification of biomarkers at concentrations as low as 10 femtograms per milliliter.

Schematic illustration of the iMEP assay for blood exosomal biomarkers

The iMEP system integrates the immunomagnetic enrichment of blood exosomes, immunorecognition of exosomal biomarkers, and real-time PCR. Antibody and DNA were conjugated and purified to produce DNA-antibody conjugates. To profile low-abundance AD biomarkers on exosomes by iMEP, DNA-antibody conjugates were incubated with immunomagnetically enriched blood exosomes followed by real-time PCR. Because exosomes contain multiple AD biomarkers, the levels of different biomarkers could be detected on the same sample after combining DNA-antibody conjugates of different biomarkers with exosomes. The iMEP system combines the specificity of antibodies and the sensitivity of PCR to improve the accuracy of femtomolar concentrations detection. The iMEP assay exhibits an average sensitivity of approximately 87.5% in distinguishing patients with AD from healthy individuals.

The results of the study demonstrate the superiority of exosomal Aβ1–42 in distinguishing individuals with AD from healthy counterparts compared to exosomal p-tau181 and p-tau396,404. With an impressive sensitivity of 95.0% and specificity of 95.0%, the iMEP assay provides a highly accurate diagnostic tool for AD.

Furthermore, the iMEP technique offers the capability to quantify levels of various exosomal biomarkers associated with the pathogenesis of AD, providing valuable insights into disease progression and potential therapeutic targets.

This groundbreaking research signifies a significant advancement in the field of neurodegenerative disease diagnosis. By harnessing the potential of blood exosomes and leveraging cutting-edge technology, the iMEP platform holds tremendous promise for improving the early detection and management of Alzheimer’s disease, ultimately enhancing patient outcomes and quality of life.

Hu S, Zhang L, Su Y, Liang X, Yang J, Luo Q, Luo H. (2024) Sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer’s disease. Sci Adv 10(13):eabm3088. [article]

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