Kim Y, Yoo YK, Kim HY, Roh JH, Kim J, Baek S, Lee JC, Kim HJ, Chae MS, Jeong D, Park D, Lee S, Jang H, Kim K, Lee JH, Byun BH, Park SY, Ha JH, Lee KC, Cho WW, Kim JS, Koh JY, Lim SM, Hwang KS. Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system. Sci Adv. 2019 Apr;5(4):eaav1388. Epub 2019 Apr 17 PubMed.

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  1. The authors have developed a microfluidics-based, solid-state impedance measure (interdigitated microelectrode [IME] sensor system) of monoclonal antibody 6E10-Aβ interactions which they claim can measure plasma Aβ levels on a scale of 0.1 pg/ml. The results appear very preliminary, with only small numbers of test subjects from two Korean sites (n=53 at each) and roughly equal numbers of subjects with normal cognition (NC) and persons with AD dementia. One site used florbetaben-PET and the other used an unvalidated tracer FC119S for screening of participants.

    The plasma assay depends on the effects of adding the small molecule hydroxyethyl-piperazinepropanesulfonic acid (EPPS), which is intended to dissociate Aβ complexes and aggregates, thus allowing an assay for total plasma Aβ. The results show an increased signal in the AD group, but the sample numbers are too small to allow any conclusions on performance of detecting Aβ-positive subjects in the CN groups. Much more work is required to demonstrate specificity for the various stages of AD throughout its 30-year natural history of onset and progression.

    This assay therefore joins with the Taiwanese MagQu test (Immuno-Magnetic Reduction–Superconducting Quantum Interference [IMR-SQUID] technique, Yang et al., 2017) in that both are showing increased signals in AD, whereas most other high-performance assays (mass spectrometric and immunoassays) are driven by a decrease in the Aβ42 signal. This is a paradox which remains to be resolved. The answer may contain some important insights into AD pathogenesis.

    References:

    Yang SY, Chiu MJ, Chen TF, Horng HE. Detection of Plasma Biomarkers Using Immunomagnetic Reduction: A Promising Method for the Early Diagnosis of Alzheimer's Disease. Neurol Ther. 2017 Jul;6(Suppl 1):37-56. Epub 2017 Jul 21 PubMed.

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