. 2021 Oct 21;5(1):761-770.

doi: 10.3233/ADR-210310. eCollection 2021.

Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study

Chaur-Jong Hu^{1

2

3

4}, Ming-Jang Chiu^{5

6

7

8}, Ming-Chyi Pai⁹, Sui-Hing Yan¹⁰, Pei-Ning Wang^{11

12

13}, Pai-Yi Chiu^{14

15}, Chin-Hsien Lin⁵, Ta-Fu Chen⁵, Fu-Chi Yang¹⁶, Kuo-Lun Huang¹⁷, Yi-Ting Hsu¹⁸, Yi-Chou Hou^{19

20

21}, Wei-Che Lin²², Cheng-Hsien Lu²³, Li-Kai Huang^{1

2}, Shieh-Yueh Yang²⁴

Affiliations

¹ Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Neurology, Dementia Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
³ Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁴ Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Department of Psychology, National Taiwan University, Taipei, Taiwan.
⁸ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
⁹ Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹⁰ Department of Neurology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
¹¹ Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
¹² Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹³ Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
¹⁴ Department of Neurology, Show Chwan Memorial Hospital, Chunghwa, Taiwan.
¹⁵ MR-guided Focus Ultrasound Center, Chang Bin Show Chwan Memorial Hospital, Chunghwa, Taiwan.
¹⁶ Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁷ Department of Neurology, Linkou Chang Gung Memorial Hospital, and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁸ Department of Neurology, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁹ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
²⁰ Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan.
²¹ School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
²² Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
²³ Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
²⁴ MagQu Co., Ltd., New Taipei City, Taiwan.

PMID: 34870102
PMCID: PMC8609520
DOI: 10.3233/ADR-210310

Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study

Chaur-Jong Hu et al. J Alzheimers Dis Rep. 2021.

. 2021 Oct 21;5(1):761-770.

doi: 10.3233/ADR-210310. eCollection 2021.

Authors

Affiliations

¹ Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Neurology, Dementia Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
³ Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁴ Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Department of Psychology, National Taiwan University, Taipei, Taiwan.
⁸ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
⁹ Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹⁰ Department of Neurology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
¹¹ Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
¹² Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹³ Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
¹⁴ Department of Neurology, Show Chwan Memorial Hospital, Chunghwa, Taiwan.
¹⁵ MR-guided Focus Ultrasound Center, Chang Bin Show Chwan Memorial Hospital, Chunghwa, Taiwan.
¹⁶ Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁷ Department of Neurology, Linkou Chang Gung Memorial Hospital, and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁸ Department of Neurology, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁹ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
²⁰ Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan.
²¹ School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
²² Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
²³ Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
²⁴ MagQu Co., Ltd., New Taipei City, Taiwan.

PMID: 34870102
PMCID: PMC8609520
DOI: 10.3233/ADR-210310

Abstract

Background: In Alzheimer's disease (AD), cognitive impairment begins 10-15 years later than neurodegeneration in the brain. Plasma biomarkers are promising candidates for assessing neurodegeneration in people with normal cognition. It has been reported that subjects with the concentration of plasma amyloid-β 1-42×total tau protein higher than 455 pg²/ml² are assessed as having a high risk of amnesic mild impairment or AD, denoted as high risk of AD (HRAD).

Objective: The prevalence of high-risk for dementia in cognitively normal controls is explored by assaying plasma biomarkers.

Methods: 422 subjects with normal cognition were enrolled around Taiwan. Plasma Aβ_1-40, Aβ_1-42, and T-Tau levels were assayed using immunomagnetic reduction to assess the risk of dementia.

Results: The results showed that 4.6% of young adults (age: 20-44 years), 8.5% of middle-aged adults (age: 45-64 years), and 7.3% of elderly adults (age: 65-90 years) had HRAD. The percentage of individuals with HRAD dramatically increased in middle-aged and elderly adults compared to young adults.

Conclusion: The percentage of HRAD in cognitively normal subjects are approximately 10%, which reveals that the potentially public-health problem of AD in normal population. Although the subject having abnormal levels of Aβ or tau is not definitely going on to develop cognitive declines or AD, the risk of suffering cognitive impairment in future is relatively high. Suitable managements are suggested for these high-risk cognitively normal population. Worth noting, attention should be paid to preventing cognitive impairment due to AD, not only in elderly adults but also middle-aged adults.

Keywords: Alzheimer’s disease; immunomagnetic reduction; normal cognition; plasma biomarkers.

PubMed Disclaimer

Conflict of interest statement

SY Yang is an employee and a shareholder of MagQu Co., Ltd. Other authors do not have conflicts of interest.

Figures

**Fig. 1**
Age-dependent concentrations of plasma (a) Aβ_1-40, (b) Aβ_1-42, and (c) T-Tau in females (gray dots) and males (dark gray dots).

**Fig. 2**
Percentage of (a) high risk for amnesic mild impairment or AD (HRAD) and (b) subhealth in cognitively normal subjects in young adults, middle-aged adults and old adults.

**Fig. 3**
Gaussian distributions of concentrations of (a) Aβ_1-40, (b) Aβ_1-42, and (c) T-Tau in plasma in cognitively normal subjects. The solid lines are the fitted Equation (1). The values of fitting parameters are shown in Table 3.

See this image and copyright information in PMC

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Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study

Affiliations

Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study

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Abstract

Conflict of interest statement

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