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

Lih Fen Lue, Ming Chyi Pai, Ta Fu Chen, Chaur Jong Hu, Li Kai Huang, Wei Che Lin, Chau Chung Wu, Jian Shing Jeng, Kaj Blennow, Marwan N. Sabbagh, Sui Hing Yan, Pei Ning Wang, Shieh Yueh Yang, Hiroyuki Hatsuta, Satoru Morimoto, Akitoshi Takeda, Yoshiaki Itoh, Jun Liu, Haiqun Xie, Ming Jang Chiu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number222
JournalFrontiers in Aging Neuroscience
Volume11
DOIs
Publication statusPublished - 2019 Sep 3

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Biomarkers
Age Groups
Alzheimer Disease
Neurofibrillary Tangles
Amyloid Plaques
North America
Amyloid
Cognition
Multicenter Studies
Longitudinal Studies
Dementia
Guidelines
Brain

All Science Journal Classification (ASJC) codes

  • Ageing
  • Cognitive Neuroscience

Cite this

Lue, Lih Fen ; Pai, Ming Chyi ; Chen, Ta Fu ; Hu, Chaur Jong ; Huang, Li Kai ; Lin, Wei Che ; Wu, Chau Chung ; Jeng, Jian Shing ; Blennow, Kaj ; Sabbagh, Marwan N. ; Yan, Sui Hing ; Wang, Pei Ning ; Yang, Shieh Yueh ; Hatsuta, Hiroyuki ; Morimoto, Satoru ; Takeda, Akitoshi ; Itoh, Yoshiaki ; Liu, Jun ; Xie, Haiqun ; Chiu, Ming Jang. / Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects. In: Frontiers in Aging Neuroscience. 2019 ; Vol. 11.
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abstract = "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.",
author = "Lue, {Lih Fen} and Pai, {Ming Chyi} and Chen, {Ta Fu} and Hu, {Chaur Jong} and Huang, {Li Kai} and Lin, {Wei Che} and Wu, {Chau Chung} and Jeng, {Jian Shing} and Kaj Blennow and Sabbagh, {Marwan N.} and Yan, {Sui Hing} and Wang, {Pei Ning} and Yang, {Shieh Yueh} and Hiroyuki Hatsuta and Satoru Morimoto and Akitoshi Takeda and Yoshiaki Itoh and Jun Liu and Haiqun Xie and Chiu, {Ming Jang}",
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month = "9",
day = "3",
doi = "10.3389/fnagi.2019.00222",
language = "English",
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Lue, LF, Pai, MC, Chen, TF, Hu, CJ, Huang, LK, Lin, WC, Wu, CC, Jeng, JS, Blennow, K, Sabbagh, MN, Yan, SH, Wang, PN, Yang, SY, Hatsuta, H, Morimoto, S, Takeda, A, Itoh, Y, Liu, J, Xie, H & Chiu, MJ 2019, 'Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects', Frontiers in Aging Neuroscience, vol. 11, 222. https://doi.org/10.3389/fnagi.2019.00222

Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects. / Lue, Lih Fen; Pai, Ming Chyi; Chen, Ta Fu; Hu, Chaur Jong; Huang, Li Kai; Lin, Wei Che; Wu, Chau Chung; Jeng, Jian Shing; Blennow, Kaj; Sabbagh, Marwan N.; Yan, Sui Hing; Wang, Pei Ning; Yang, Shieh Yueh; Hatsuta, Hiroyuki; Morimoto, Satoru; Takeda, Akitoshi; Itoh, Yoshiaki; Liu, Jun; Xie, Haiqun; Chiu, Ming Jang.

In: Frontiers in Aging Neuroscience, Vol. 11, 222, 03.09.2019.

Research output: Contribution to journalArticle

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

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.

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