Combined Plasma Biomarkers for Diagnosing Mild Cognition Impairment and Alzheimer’s Disease

Abstract

A highly sensitive immunoassay, the immunomagnetic reduction, is used to measure several biomarkers for plasma that is related to Alzheimer's disease (AD). These biomarkers include Aβ-40, Aβ-42, and tau proteins. The samples are composed of four groups: healthy controls (n = 66), mild cognitive impairment (MCI, n = 22), very mild dementia (n = 23), and mild-toserve dementia, all due to AD (n = 22). It is found that the concentrations of both Aβ-42 and tau protein for the healthy controls are significantly lower than those of all of the other groups. The sensitivity and the specificity of plasma Aβ-42 and tau protein in differentiating MCI from AD are all around 0.9 (0.88−0.97). However, neither plasma Aβ-42 nor tau-protein concentration is an adequate parameter to distinguish MCI from AD. A parameter is proposed, which is the product of plasma Aβ-42 and tau-protein levels, to differentiate MCI from AD. The sensitivity and specificity are found to be 0.80 and 0.82, respectively. It is concluded that the use of combined plasma biomarkers not only allows the differentiation of the healthy controls and patients with AD in both the prodromal phase and the dementia phase, but it also allows AD in the prodromal phase to be distinguished from that in the dementia phase.

Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood

“…A recent study reported elevated T-tau levels in AD patients compared with MCI and controls but found significant overlap between MCI and AD as well as no correlation between tau levels in CSF and plasma (44). Another study reported increased level of T-tau protein in AD, which when combined with the levels of Aβ-42, achieved improved sensitivities and specificities (80 and 82%, respectively) in differentiation of MCI from AD (45). The above-mentioned metaanalysis (43) also concluded that increased plasma level of T-tau was the only blood biomarker that discriminated AD from controls; however, it was pointed out that this finding would need additional verification in larger cohorts.…”

Blood Biomarkers for Alzheimer’s Disease: Much Promise, Cautious Progress

“…One of these studies showed a significant inverse effect [ 34 ] and one showed no appreciable effect [ 35 ]-both used conventional ELISA methods that were not optimised to measure the low concentrations of tau in the blood. A more sensitive immunomagnetic reduction method was used in three other comparisons derived from two studies by the same group [ 36,37 ] and showed effect sizes consistent with the results of the overall meta-analysis, but these results, using this particular measurement technique, are in need of independent replication. The final study [ 38 ] utilised a single molecular digital array platform that is able to quantify t-tau at the single molecule level and proved to have the highest sensitivity of the three methods [ 39 ].…”

Quantitative analysis of total β-subunit of human chorionic gonadotropin concentration in urine by immunomagnetic reduction to assist in the diagnosis of ectopic pregnancy

“…However, the reaction time could be accelerated to within 30 minutes by properly adjusting laboratory factors, such as reagent concentration, reagent/hCGβ solution volume, and incubation temperature. 31,32 Third, the number of clinical samples in this study was limited, and a larger sample size is necessary to support our preliminary results. Furthermore, a high urine hCGβ IMR signal or serial measurements of increased urine hCGβ IMR signals are not the only cornerstone of a clinical decision of ectopic pregnancy, and should be combined with transvaginal ultrasound scans.…”

“…23,[29][30][31] This is the pioneering investigation of using an IMR assay to measure biomarkers in urine, and our findings imply that the IMR assay is a potential candidate for point-of-care testing to assist in the diagnosis of ectopic pregnancy.…”