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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00222

Age-Dependent Relationship between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects

 Lih-Fen Lue1, Ming-Chyi Pai2,  Ta-Fu Chen3,  Chaur-Jong Hu4, 5,  Li-Kai Huang4, 5,  Wei-Che Lin6,  Chau-Chung Wu7,  Jiann-Shing Jeng3,  Kaj Blennow8, 9,  Marwan N. Sabbagh10, Sui-Hing Yan11,  Pei-Ning Wang12, 13,  Shieh-Yueh Yang14, 15, Hiroyuki Hatsuta16, 17,  Satoru Morimoto16, 18,  Akitoshi Takeda17, Yoshiaki Itoh17, Jun Liu19,  Haiqun Xie20 and  Ming-Jang Chiu21*
  • 1Banner Sun Health Research Institute, United States
  • 2National Cheng Kung University, Taiwan
  • 3Department of Neurology, National Taiwan University Hospital, Taiwan
  • 4Taipei Medical University, Taiwan
  • 5Shuang Ho Hospital, Taipei Medical University, Taiwan
  • 6Kaohsiung Chang Gung Memorial Hospital, Taiwan
  • 7Department of Internal medicine, National Taiwan University Hospital, Taiwan
  • 8Sahlgrenska University Hospital, Sweden
  • 9University of Gothenburg, Sweden
  • 10Lou Ruvo Center for Brain Health, Cleveland Clinic, United States
  • 11Taipei City Hospital, Taiwan
  • 12National Yang-Ming University, Taiwan
  • 13Taipei Veterans General Hospital, Taiwan
  • 14MagQu, Taiwan
  • 15MagQu LLC, United States
  • 16Hatsuta Neurology Clinic, Japan
  • 17Department of Neurology, Osaka City University, Japan
  • 18Department of physiology, School of Medicine, Keio University, Japan
  • 19Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China
  • 20Department of Neurology, First People's Hospital of Foshan, China
  • 21National Taiwan University, Taiwan

Both amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with Alzheimer’s disease (AD). However, the constituents of these hallmarks, amyloid beta (Aβ) 40, Aβ42, and total Tau (t-Tau), have been detected in the blood of cognitively normal subjects by using an immunomagnetic reduction (IMR) assay. Whether these levels are age dependent is not known, and their interrelation remains undefined. We determined the levels of these biomarkers in cognitively normal subjects of different age groups.
A total of 391 cognitively normal subjects aged 23 to 91 were enrolled from hospitals in Asia, Europe, and North America. Healthy cognition was evaluated by NIA-AA guidelines to exclude subjects with mild cognitive impairment (MCI) and AD and by cognitive assessment using the Mini Mental State Examination and Clinical Dementia Rating. We examined the effect of age on plasma levels of Aβ40, Aβ42, and t-Tau and the relationship between these biomarkers during aging. Additionally, we explored age-related reference intervals for each biomarker. Plasma t-Tau and Aβ42 levels had modest but significant correlations with chronological age (r = 0.127, p = 0.0120 for t-Tau; r = -0.126, p = 0.0128 for Aβ42), ranging from ages 23 to 91. Significant positive correlations were detected between Aβ42 and t-Tau in the groups aged 50 years and older, with Rho values ranging from 0.249 to 0.474. Significant negative correlations were detected between Aβ40 and t-Tau from age 40 to 91 (r ranged from -0.293 to -0.582) and between Aβ40 and Aβ42 in the age groups of 30-39 (r = -0.562, p = 0.0235), 50-59 (r = -0.261, p = 0.0142), 60-69 (r = -0.303, p = 0.0004), and 80-91 (r = 0.459, p = 0.0083). We also provided age-related reference intervals for each biomarker. In this multicenter study, age had weak but significant effects on the levels of Aβ42 and t-Tau in plasma. However, the age group defined by decade revealed the emergence of a relationship between Aβ40, Aβ42, and t-Tau in the 6th and 7th decades. Validation of our findings in a large-scale and longitudinal study is warranted.

Keywords: Immunomagnetic reduction, tau, Amyloid, Plasma, Alzheimer, Cognitively normal subjects

Received: 15 Apr 2019; Accepted: 06 Aug 2019.

Copyright: © 2019 Lue, Pai, Chen, Hu, Huang, Lin, Wu, Jeng, Blennow, Sabbagh, Yan, Wang, Yang, Hatsuta, Morimoto, Takeda, Itoh, Liu, Xie and Chiu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Ming-Jang Chiu, National Taiwan University, Taipei, Taiwan, mjchiu@ntu.edu.tw