Prediction of Cerebral Amyloid Pathology Based on Plasma Amyloid and Tau Related Markers

Ting-Bin Chen; Kun-Ju Lin; Szu-Ying Lin; Yi-Jung Lee; Yi-Cheng Lin; Chen-Yu Wang; Jun-Peng Chen; Pei-Ning Wang

doi:10.3389/fneur.2021.619388

Prediction of Cerebral Amyloid Pathology Based on Plasma Amyloid and Tau Related Markers

Front Neurol. 2021 Oct 4:12:619388. doi: 10.3389/fneur.2021.619388. eCollection 2021.

Authors

Ting-Bin Chen^{1

2

3}, Kun-Ju Lin^{4

5}, Szu-Ying Lin⁶, Yi-Jung Lee⁷, Yi-Cheng Lin^{6

8}, Chen-Yu Wang⁹, Jun-Peng Chen¹⁰, Pei-Ning Wang^{9

11

12}

Affiliations

¹ Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan.
² Dementia Center, Taichung Veterans General Hospital, Taichung, Taiwan.
³ Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan.
⁴ Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan.
⁷ Division of Neurology, Department of Medicine, Taipei City Hospital Renai Branch, Taipei, Taiwan.
⁸ School of Life Sciences, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
⁹ Division of General Neurology, Department of Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁰ Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan.
¹¹ Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹² Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

Background and Purpose: Pyroglutamate-modified β-amyloid peptide (Aβ_pE) is crucial for AD pathophysiological process. The potential associations of plasma Aβ_pE and total tau (t-tau) with brain Aβ burden and cognitive performance remain to be clarified. Methods: Forty-six subjects with unimpaired cognition, mild cognitive impairment, or very mild dementia were enrolled. Plasma levels of Aβ_pE3-40, t-tau, and Aβ42 were quantified by immunomagnetic reduction (IMR) assays. We analyzed individual and combined biomarker correlations with neuropsychological scores and Aβ positivity determined by ¹⁸F-florbetapir positron emission tomography (PET). Results: Both plasma Aβ_pE3-40 levels and Aβ_pE3-40/t-tau ratios correlated negatively with short-term memory and global cognition scores, while correlating positively with PET standardized uptake value ratios (SUVRs). Among the biomarkers analyzed, the combination of Aβ_pE3-40 in a ratio with t-tau had the best discriminatory ability for Aβ PET positivity. Likewise, logistic regression analysis showed that Aβ_pE3-40/t-tau was a highly robust predictor of Aβ PET positivity after controlling for relevant demographic covariates. Conclusion: Plasma Aβ_pE3-40/t-tau ratios correlate with cognitive function and cerebral Aβ burden. The suitability of Aβ_pE3-40/t-tau as a candidate clinical biomarker of AD pathology in the brain should be examined further in larger studies.

Keywords: Alzheimer's disease; predictor; pyroglutamate; tau; β-amyloid.