TY - JOUR
T1 - Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects
AU - Lue, Lih Fen
AU - Pai, Ming Chyi
AU - Chen, Ta Fu
AU - Hu, Chaur Jong
AU - Huang, Li Kai
AU - Lin, Wei Che
AU - Wu, Chau Chung
AU - Jeng, Jian Shing
AU - Blennow, Kaj
AU - Sabbagh, Marwan N.
AU - Yan, Sui Hing
AU - Wang, Pei Ning
AU - Yang, Shieh Yueh
AU - Hatsuta, Hiroyuki
AU - Morimoto, Satoru
AU - Takeda, Akitoshi
AU - Itoh, Yoshiaki
AU - Liu, Jun
AU - Xie, Haiqun
AU - Chiu, Ming Jang
N1 - Funding Information:
Funding. We acknowledge the funding support of the Arizona Alzheimer Consortium for the study conducted in the United States, Ulvac Inc., for the study conducted in Osaka and Innovative Biotechnology Limited for the study conducted in Foshan and Guangzhou. The study conducted in National Taiwan University Hospital was supported in part by National Health Research Institutes, Taiwan (05A1-PHSP03-028) and in part by Ministry of Science and Technology Taiwan (106~108-2321-B-002-018,075,002).
Publisher Copyright:
© Copyright © 2019 Lue, Pai, Chen, Hu, Huang, Lin, Wu, Jeng, Blennow, Sabbagh, Yan, Wang, Yang, Hatsuta, Morimoto, Takeda, Itoh, Liu, Xie and Chiu.
PY - 2019/9/3
Y1 - 2019/9/3
N2 - 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 23–91 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 (CDR). 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.
AB - 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 23–91 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 (CDR). 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.
KW - Alzheimer
KW - amyloid
KW - cognitively normal subjects
KW - immunomagnetic reduction
KW - plasma
KW - tau
UR - http://www.scopus.com/inward/record.url?scp=85072836879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072836879&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2019.00222
DO - 10.3389/fnagi.2019.00222
M3 - Article
AN - SCOPUS:85072836879
SN - 1663-4365
VL - 11
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 222
ER -