Nanoparticle-based immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer's disease – A cross-validation study

• Published in: Nanomedicine 2020-08, Vol.28, p.102182-102182, Article 102182
• Main Authors: Chiu, Ming-Jang, Chen, Ta-Fu, Hu, Chaur-Jong, Yan, Sui-Hing, Sun, Yu, Liu, Bing-Hsien, Chang, Yun-Tsui, Yang, Che-Chuan, Yang, Shieh-Yueh
• Format: Article
• Language: English
• Subjects: Blood-based biomarkers; Immunomagnetic reduction assay; Mild cognitive impairment; Plasma Aβ1–42; Plasma tau
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102182

Blood-based biomarker assays of plasma β-amyloid (Aβ) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines. The cutoff value for plasma Aβ1–42 (16.4 pg/ml) performed the best in differentiating between controls and patients with prodromal or clinical AD, with 92.5% for positive percent agreement (PPA), negative percent agreement (NPA), and overall rate of agreement (ORA). Aβ1–42 × tau (642.58) was useful for separating patients with dementia and prodromal states of AD, with 84.9% PPA, 78.8% NPA and 83% ORA. The figure demonstrates system and methods used in this report. In the upper part of the center, there is a SQUID-based magnetometer consisting of both excitation and pickup coils. The left upper part shows signals of the reagent before mixing the sample solution containing Aβ1–40, Aβ1–42 and tau protein. The right upper part shows an example by mixing plasma sample from a control subject whose plasma sample containing relative low levels of the pathological proteins compared to the right lower part, which mixed plasma sample with higher levels from a subject with dementia due to Alzheimer's disease. After bindings of the molecules of the pathological proteins, the signals start to decline because of the spin velocities of the magnetic nanoparticles decreased resulting the signal reduction demonstrated in the lower part of the center. Left lower shows images of biofunctionalized nano-particles of a scanning electron microscope. [Display omitted]