Interview with Professor Chen Xiaochun and Du Yifeng: Blood biomarkers can predict amyloid deposition, and the future can be expected!

As a common neurodegenerative disease, Alzheimer's disease (AD) has become a major disease that seriously endangers human health with its high incidence, high prevalence, high mortality and high disease burden

In 2018, under the leadership of Professor Shen Yong from the First Affiliated Hospital of the University of Science and Technology of China and under the guidance of many experts in the field at home and abroad, the "China Aging and Neurodegenerative Disease Research Cohort (CANDI)" was officially launched

This article mainly organizes the research content of CANDI.

Introduction to CANDI Research

Research Background

At present, the detection of AD is mainly based on neurological function scale cognitive assessment, imaging examination (PET-CT, MRI, etc.

Research methods

A total of 411 patients were included in the study, including 96 cognitively normal individuals, 94 patients with mild cognitive impairment (MCI), 173 patients with a clinical diagnosis of AD, and 48 patients with a clinical diagnosis of non-AD dementia

Research result

1.

➤ When using multiple plasma biomarkers to predict Aβ deposition status, p-tau181 + apolipoprotein E (APOE) + MRI can achieve high accuracy

Figure 2 Model selection process and performance for predicting brain Aβ status in CANDI

Analysis conclusion

The results of this study show that when using a single plasma biomarker to predict Aβ deposition status, p-tau181 can achieve higher accuracy; when using multiple plasma biomarkers to predict Aβ deposition status, p-tau181+APOE+MRI can achieve higher accuracy High accuracy
.

The results reveal the general applicability of AD blood biomarker detection in the Chinese population and provide an effective and cost-effective diagnostic model for the early diagnosis of AD in China in the future
.

Expert interpretation

Professor Chen Xiaochun

• Professor, Chief Physician and Doctoral Supervisor of Department of Neurology, Union Hospital Affiliated to Fujian Medical University

• Vice Chairman of Fujian Association of Science and Technology, President of Fujian Medical Association

• Executive Director of Chinese Medical Doctor Association, President-elect of Neurology Branch

• Head of Dementia and Cognitive Impairment Group, Neurology Branch of Chinese Medical Association

• He has long been engaged in the clinical diagnosis and treatment and research of neurodegenerative diseases, focusing on the pathogenesis and prevention strategies of Alzheimer's disease and Parkinson's disease.
He has presided over more than 10 national research projects.
More than 80 high-quality research papers have been published in journals
.

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AD molecular imaging PET examination and CSF biological marker detection are necessary means for accurate diagnosis of AD, especially when the clinical symptoms are not obvious in the early stage of AD, the significance of biological marker detection is even more important
.

The Chinese expert consensus on the diagnosis and treatment of AD-derived MCI published in May this year - "Chinese Expert Consensus on the Diagnosis and Treatment of Alzheimer's Disease-derived Mild Cognitive Impairment 2021" ² emphasizes the importance of AD-related biology in the form of A-level evidence and I-level recommendation.
Application of biological markers in the diagnosis of AD-derived MCI
.

However, limited by the low availability and high price of molecular imaging PET examination, and the invasiveness of CSF detection, the popularization and application of AD biomarker detection in China does have some difficulties and resistance
.

Relatively speaking, the advantages of blood biomarker testing are obvious - less trauma to patients, easy access to samples, and relatively low cost
.

If the detection of AD blood biomarkers can establish a standardized detection process and a reliable reference interval suitable for the Chinese population, and its diagnostic efficacy can be fully verified, the detection of blood biomarkers will undoubtedly have a wider scope of application and application prospects.
Will significantly improve the accuracy of AD diagnosis
.

Blood biomarker testing in the CANDI cohort provides a solid foundation for achieving this goal
.

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Professor Du Yifeng

• Head of Department of Neurology, Shandong First Medical University

• Director of Department of Neurology, Shandong Provincial Hospital

• Director of Shandong Provincial Neurological Disease Clinical Research Center

• Chief Expert of National Key R&D Program

• Taishan Scholars Distinguished Expert

• Vice President of Neurology Branch of Chinese Medical Doctor Association

• Deputy Head of Dementia and Cognitive Impairment Group, Neurology Branch of Chinese Medical Association

• Deputy Editor-in-Chief of "Chinese Journal of Behavioral Medicine and Brain Science"

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At present, the detection of specific biomarkers for AD is mainly carried out by CSF detection, Aβ PET or tau PET examination.
Although these methods can be used for the accurate diagnosis of AD, they cannot be used in the diagnosis of AD due to their invasiveness, high price, and difficulty in popularization.
commonly carried out clinically
.

The early diagnosis of AD is particularly important for the early diagnosis and early treatment of AD.
The use of blood biomarkers for the early diagnosis of AD has become more and more popular in recent years, especially the emergence of single-molecule immune detection technology, which has greatly promoted the whole process of AD.
The industry's expectations for the application of blood biomarkers in the accurate diagnosis of AD
.

In the research conducted by the above-mentioned Professor Shen Yong's team, they combined the phosphorylated tau protein level in plasma, APOE genotype, and MRI to construct a simple and efficient algorithm, which can achieve non-invasive and accurate prediction of Aβ-PET Detected amyloid deposition status with comparable accuracy to CSF ​​detection
.

Therefore, this model can be used to predict the status of amyloid deposition, thereby promoting accurate diagnosis of AD based on biomarker status
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The CANDI cohort study is the first study to systematically report blood biomarker data in the Chinese population.
The results of this study show that the types of biomarkers used to predict amyloid deposition status in the Chinese population are similar to international European and American-based biomarkers.
The results of the studies are basically the same, but there are some differences in the concentration of specific biomarkers.
For example, the concentration of p-tau181 in the Chinese population is significantly lower than that in the European and American populations.
Therefore, the reference interval or judgment threshold for AD blood biomarkers in the Chinese population is established.
Clinical application is crucial
.

In addition, the article "Prediction of future Alzheimer's disease dementia using plasma phospho-tau combined with other accessible measures" published in 2021 by Oskar Hansson et ^al.
3In this study, the researchers used a similar method to construct a predictive model for the transformation of SCD/MCI population into AD-derived dementia within 4 years.
APOE typing, plasma phosphorylated tau levels combined with cognitive assessment can achieve high predictive accuracy
.

Therefore, blood biomarkers combined with APOE typing and necessary structural imaging or cognitive assessment data can realize the prediction of AD pathological changes and the prognosis of the disease, and provide an effective tool for accurate diagnosis and treatment of AD
.
References:
1.
Gao F, et al.
Alzheimers Dement.
2022 Jun 6.
doi: 10.
1002/alz.
12700.
2.
Dementia and Cognitive Impairment Group of Neurology Branch of Chinese Medical Association.
Chinese Journal of Neurology, 2022, 55(5 ):421-440.
3.
Palmqvist S, et al.
Nat Med.
2021 Jun;27(6):1034-1042.
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