The Validation of Multifactor Model of Plasma Aβ 42 and Total-Tau in Combination With MoCA for Diagnosing Probable Alzheimer Disease

Fubin Jiao; Fang Yi; Yuanyuan Wang; Shouzi Zhang; Yanjun Guo; Wenjin Du; Ya Gao; Jingjing Ren; Haifeng Zhang; Lixin Liu; Haifeng Song; Luning Wang

doi:10.3389/fnagi.2020.00212

The Validation of Multifactor Model of Plasma Aβ ₄₂ and Total-Tau in Combination With MoCA for Diagnosing Probable Alzheimer Disease

Front Aging Neurosci. 2020 Jul 21:12:212. doi: 10.3389/fnagi.2020.00212. eCollection 2020.

Authors

Fubin Jiao^{1

2

3}, Fang Yi^{2

4}, Yuanyuan Wang², Shouzi Zhang⁵, Yanjun Guo⁶, Wenjin Du⁷, Ya Gao⁸, Jingjing Ren⁹, Haifeng Zhang³, Lixin Liu⁵, Haifeng Song⁹, Luning Wang^{1

2}

Affiliations

¹ Medical School of Chinese People's Liberation Army, Beijing, China.
² Department of Neurology, The 2nd Medical Center, National Clinical Research Center for Geriatric Disease, Chinese People's Liberation Army General Hospital, Beijing, China.
³ Health Service Department of the Guard Bureau of the Joint Staff Department, Joint Staff of the Central Military Commission of Chinese PLA, Beijing, China.
⁴ Department of Neurology, Lishilu Outpatient, Jingzhong Medical District, Chinese People's Liberation Army General Hospital, Beijing, China.
⁵ The Psycho Department of Beijing Geriatric Hospital, Beijing, China.
⁶ Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
⁷ Department of Neurology, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China.
⁸ Department of Geriatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
⁹ National Engineering Research Center for Protein Drugs, Beijing, China.

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, and MoCA as the variable to generate receiver operating characteristic (ROC) curve, cutoff value = 0.48, sensitivity = 0.973, specificity = 0.982, area under the curve (AUC) = 0.986, offered better categorical efficacy, sensitivity, specificity, and AUC. The multifactor model of plasma Aβ42 and t-tau in combination with MoCA can be a viable model separate health and AD subjects in clinical practice.

Keywords: Alzheimer disease; Montreal Cognitive Assessment; tau; ultrasensitive immunomagnetic reduction; β-amyloid.