The Validation of Multifactor Model of Plasma Aβ42 and Total-Tau in Combination With MoCA for Diagnosing Probable Alzheimer Disease

Abstract

Alzheimer disease (AD) has an insidious onset and heterogeneous clinical symptoms. The well-accepted biomarkers for clinical diagnosis of AD include β-amyloid (Aβ) deposition and pathologic tau level within cerebral spinal fluid (CSF) and imaging AD pathology such as positive emission tomography (PET) imaging of the amyloid-binding agent Pittsburgh compound B (PET-PiB). However, the high expense and invasive nature of these methods highly limit their wide usage in clinic practice. Therefore, it is imperious to develop less expensive and invasive methods, and plasma biomarkers are the premium targets. In the current study, we utilized a single-blind comparison method; all the probable AD cases met the core clinical National Institute on Aging and Alzheimer's Association (NIA-AA) criteria and validated by PET-PiB. We used ultrasensitive immunomagnetic reduction (IMR) assays to measure plasma Aβ 42 and total-tau (t-tau) levels, in combination with different variables including Aβ42 × t-tau value, Montreal Cognitive Assessment (MoCA), and Mini Mental State Examination (MMSE). We used logistic regression to analyze the effect of all these variables in the algorism. Our results showed that (1) plasma Aβ42 and t-tau are efficient biomarkers for AD diagnosis using IMR platform, whereas Aβ42 × t-tau value is more efficient for discriminating control and AD; (2) in the control group, Aβ42 level and age demonstrated strong negative correlation; Aβ42 × t-tau value and age demonstrated significant negative correlation; (3) in the AD group, t-tau level and MMSE score demonstrated strong negative correlation; (4) using the model that Aβ42, Aβ42 × t-tau,

Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis

“…S6). Similarly, 9 papers [72][73][74][76][77][78][79][80][81] reporting 11 cohorts using the IMR method (362 controls and 267 patients) were identified ( Fig. S5), showing an average WMD value of 24.83 (95% CI 15.70-33.96, I 2 = 98.9%, P < 0.0001).…”

“…S2). Fifteen publications [67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] reporting 20 cohorts were retrieved using IMR and two publications [82,83] reporting four cohorts were retrieved using a-EIMAF. The effect sizes (ESs) for plasma tau levels were 16.30 pg/ml (95% CI 14.61-17.99, I 2 = 92.7%, P < 0.0001, Fig.…”

Investigation of the Number of Tests Required for Assaying Plasma Biomarkers Associated with Alzheimer’s Disease Using Immunomagnetic Reduction

“…Although the concentrations of these biomarkers, such as amyloid b 1-40 (Ab 1-40 ), Ab 1-42 and total Tau protein (T-Tau), have been observed to be very low, assays of these plasma biomarkers are feasible due to the successful development of ultrasensitive assay technologies [2][3][4][5][6][7], such as immunomagnetic reduction (IMR) [7]. Many research groups have validated the clinical significance of discriminating AD or amnesic mild cognitive impairment (aMCI) from normal controls (NCs) [8][9][10]. In addition, correlations between plasma Ab 1-42 /Ab 1-40 and Ab plaques that were obtained using positron emission tomography (PET) have been demonstrated [11,12].…”

“…In previously published studies [7][8][9][10][11][12][13], biomarkers using IMR have been measured in duplicate. The original reason underlying the need for duplicate measurements using IMR was the ultralow concentrations of these plasma biomarkers, present approximately at concentrations of picograms per milliliter (pg/ml); to obtain reliable results, therefore, the measurement procedure was based on duplicate measurements.…”

Rapid assessments to differentiate dementia using plasma biomarkers in primary care: a case control study

“…The assessment of plasma biomarkers represents a convenient and cheap diagnostic method compared with the current gold standard of positron emission tomography (PET), which may allow for plasma biomarkers to be tested annually. Several papers reported by neurologists demonstrated the feasibility of assaying plasma biomarkers for identifying AD [19][20][21][22], Parkinson's disease [23][24][25], or frontotemporal dementia [26].…”