Head‐to‐head comparison of amplified plasmonic exosome Aβ42 platform and single‐molecule array immunoassay in a memory clinic cohort

Abstract

Background and purpose Various blood biomarkers reflecting brain amyloid‐β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. Methods Using the same cohort (n = 68), the performances of the single‐molecule array (Simoa) Aβ40, Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX) Aβ42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aβ+) participants. Results Compared to Simoa biomarkers, APEX‐Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre‐screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX‐Aβ42 and 48.6% for Simoa‐Aβ42/Aβ40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX‐Aβ42 pre‐screening does not increase the required number of initial participants. Conclusions With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aβ+ participants whilst halving recruitment costs.

Non-linear Character of Plasma Amyloid Beta Over the Course of Cognitive Decline in Alzheimer’s Continuum

“…Owning to the invasive procedure of CSF examination and high cost of PET image, blood-based assessments with comparable accuracy in predicting cerebral pathology of AD are urgently needed, especially in population screening. However, even previous studies demonstrated that plasma Aβ could be useful as a potential surrogate for brain Aβ pathology, the performances were not sufficient and discrepancies remained ( Janelidze et al, 2016 ; Verberk et al, 2018 ; Vergallo et al, 2019 ; De Meyer et al, 2020 ; Tanaka et al, 2021 ). In our current study, we explored the predictive values of plasma Aβ for Aβ-PET positive in NC, SCD, MCI, and dementia, respectively.…”

The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review

“…A similar technique applied by some studies is known as immunoprecipitation-free liquid chromatography-mass spectrometry (IP-free LC-MS), which measures Aβ species with mass spectrometry, but without antibody purification prior to measurement by LC-MS [22,34]. Studies that use a bead-based immunoassay, for example, the SIMOA assay or some high-sensitivity chemiluminescence assays, use beads for specific Aβ species antibody binding and indirect quantification, sometimes after amplification [20,22,28,[35][36][37][38][39][40]. In contrast, other studies apply plate-based immunoassays (such as an ELISA assay), in which a binding antibody is adsorbed onto a plate where it binds the Aβ species, and a second antibody binds to another Aβ antigen, forming what is known as a "sandwich" between the two antibodies [22,25,28,36].…”

“…In general, the immunoassays displayed lower AUCs across most studies that used a PET reference standard. Studies using a SIMOA assay had a weighted average AUC value of 0.690 across ten cohorts [20,22,24,28,[35][36][37], chemiluminescence assays had a weighted average AUC of 0.818 across six cohorts [22,28,38,40], IP-free LC-MS assays had a weighted average AUC of 0.742 across five cohorts [22,34], and ELISA assays had a weighted average AUC of 0.734 across three cohorts [22,25,36] (Table 1, Fig. 3).…”

“…Current guidelines do not recommend predictive testing for asymptomatic patients yet, especially without treatment or prevention options to act on [ 41 ]. It has been shown that screening patients with plasma Aβ42/40 could reduce the number of amyloid PET scans required by approximately 49–64% [ 18 , 20 , 25 , 37 , 39 ]. In addition to the economic benefits to the patient and healthcare community, an accurate blood biomarker test enables wide-scale testing of more diverse populations.…”

Changes of plasma Aβ and t-tau along with 18F-florbetapir PET in a cohort of cognitive decline

“…Previous studies demonstrated that plasma amyloid-β examined using the Simoa immunoassay could be useful as a potential surrogate for brain Aβ pathology, though the performances were not su cient and discrepancies remained (6,7,9,38,39). In the present study, relationships between plasma amyloid-β and 18F-orbetapir SUVR were assessed not only in all the subjects with Aβ-PET scan, but also in subjects with different Aβ-PET status.…”