Plasma Amyloid Concentration in Alzheimer’s Disease: Performance of a High-Throughput Amyloid Assay in Distinguishing Alzheimer’s Disease Cases from Controls

Abstract

Background: Collection of cerebrospinal fluid (CSF) for measurement of amyloid-␤ (A␤) species is a gold standard in Alzheimer's disease (AD) diagnosis, but has risks. Thus, establishing a low-risk blood A␤ test with high AD sensitivity and specificity is of outmost interest. Objective: We evaluated the ability of a commercially available plasma A␤ assay to distinguish AD patients from biomarkerhealthy controls. Method: In a case-control design, we examined plasma samples from 44 AD patients (A + N+) and 49 controls (A-N-) from a memory clinic. AD was diagnosed using a combination of neuropsychological examination, CSF biomarker analysis and brain imaging. Total A␤ 40 and total A␤ 42 in plasma were measured through enzyme-linked immunosorbent assay (ELISA) technology using ABtest40 and ABtest42 test kits (Araclon Biotech Ltd.). Receiver operating characteristic (ROC) analyses with outcome AD were performed, and sensitivity and specificity were calculated.

Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition

“…3 ). Furthermore, the diagnostic accuracy of our developed kit is comparable or superior to those from other tests using well-known plasma AD biomarkers such as plasma Aβ42/40 ratio, Aβ40/42 ratio, or plasma phosphorylated-tau (p-tau) (Supplementary Table 1) [ 3 , 24 – 32 ]. First, the AUC value from Model III (0.891 with 80.0% sensitivity and 83.0% specificity; the model with ApoE covariate) was the highest rank among the models using ApoE as a covariate (1st out of 3 biomarkers).…”

Modelling the efficacy of Neprilysin from various species in degrading different Amyloid-β peptides: Potential application in therapeutics of Alzheimer’s disease

“…The neprilysin-Amyloidβ (Aβ) was selected as the enzyme-substrate prototype as recent studies have indicate the potential role of developing recombinant neprilysin as a therapeutic candidate for treating Alzheimer's disease (AD). 2,6,8,9,16 Therapeutic development of neprilysin for use in treating AD will require establishing the optimal enzyme kinetics against AD specific Aβ peptides. 2,8,9 Although the association Aβ peptides in the progression of AD is well established, developing effective treatment will require specific and selective cleaving of a variety of Aβ peptides.…”

“…The neprilysin- Amyloidβ (Aβ) was selected as the enzyme-substrate prototype as recent studies have indicate the potential role of developing recombinant neprilysin as a therapeutic candidate for treating Alzheimer’s disease (AD). 2, 6, 8, 9, 16…”

“…The enzyme kinetics of 5JMY and Amyloid β1-40 interactions are extensively reported in the literature and forms the basis of several commercially available kits to assess neprilysin activity. 1, 6, 8, 14–16 Hence the enzymatic cleaving of Amyloid β1-40 (at a substrate concentration of 0.625, 1.25, 2.5, 5, 10, 15 and 20 μM) was studied in presence of 5 nM concentration of recombinant neprilysin (5JMY). The resultant enzyme-substrate kinetic curve was used for modelling the kinetics of rest of the Amyloid β (4XFO, 5TPT, 3SGP, 2ROZ, 2YT1, 4YN0, 2KJ7, 1NMJ, 4DBB, 2BFI, 2ONX, Aβ1-40) and neprilysin (5JMY, 6GID, 4XBH and 6GHX) combinations.…”

“…The enzyme kinetics of 5JMY and Amyloid β 1-40 interactions are extensively reported in the literature and forms the basis of several commercially available kits to assess neprilysin activity. 1,6,8,[14][15][16] Hence the enzymatic cleaving of Amyloid…”