Add a new proof – the combination of multiple blood biomarkers is expected to be an effective method for early identification of AD!

At present, about 50 million people worldwide suffer from dementia, with an average of 1 new case of dementia every 3 seconds

The onset of Alzheimer's disease is hidden, and studies have found that pathophysiological changes

Last year, a cross-sectional study titled "Performance of Plasma Amyloid β, Total Tau, and Neurofilament Light Chain in the Identification of Probable Alzheimer's Disease in South China"¹ Blood biomarker levels, including Aβ42, Aβ40, t-tau, and neural filament light chain (NfL), were measured in 277 AD patients and 153 healthy controls with normal cognitive function from southern China to assess the efficacy

Overview of the study

A total of 430 participants enrolled between March 2017 and December 2019 were included, including 277 patients with AD (AD group) and 153 healthy controls with normal cognitive function (CN group

Before correcting for confounding factors, all detected plasma biomarkers, including Aβ42, Aβ40, Aβ42/Aβ40, t-tau, and NfL, differed

After adjusting for age, sex, and APOE (apolipoprotein E) alleles, plasma t-tau and NfL levels in the AD group were significantly higher than those in the CN group (p<0.

Figure 1: Comparison of blood biomarker levels in the AD and CN groups

To understand whether plasma biomarkers effectively respond to changes in pathology in brain tissue, the study analyzed the correlation between

Table 1: Correlation analysis of blood biomarkers and cerebrospinal fluid biomarkers in AD patients * The correlation difference between biomarkers was statistically significant (p<0.

➤Combined models of age, sex, and APOE alleles showed the best diagnostic efficacy in AD recognition

Finally, in order to evaluate the diagnostic efficacy of plasma markers on AD, the researchers conducted a ROC analysis of the diagnostic accuracy of plasma markers with statistical differences

Figure 2: ROC curve analysis of blood biomarkers for AD diagnosis

Table 2: Efficacy analysis of blood biomarkers for AD diagnosis

Conclusions of the study

Although it is still challenging to accurately diagnose AD using blood biomarkers, the combination of multiple blood biomarkers may be a noninvasive and effective method

Expert Profiles

• Professor, First-level Chief Physician, Doctoral Student/Postdoctoral Supervisor

• Jiang Scholar of the Ministry of Education, Chief Scientist of the National Key R&D Program

• Director of the Department of Neurology, Xiangya Hospital, Central South University

• Deputy Director of the National Clinical Research Center for Geriatric Diseases (Xiangya Hospital).
  

• Director of Hunan Provincial Engineering Center for Cognitive Impairment

• Director of Hunan Provincial International Science and Technology Cooperation and Innovation Base for Precision Diagnosis and Treatment of Neurodegenerative Diseases and Genetic Diseases

• Executive Editor, International Journal of Neurology neurosurgery

• Deputy Leader of neuropsychology and behavioral neurology group of neurology branch of Chinese Medical Association

• Member of the Geriatric Neurology Group of the Geriatrics Branch of the Chinese Medical Association

• Vice Chairman of the Neurodegenerative Diseases Professional Committee of the Chinese Society of Microcirculation

• Member of the Standing Committee of the Cognitive Impairment Branch of the Chinese Geriatrics Society

• Member of the Standing Committee of the Vascular Cognitive Impairment Branch of the Stroke Society of China

• He led 1 national key research and development program (22.
  19 million), 1 project, and 8 national natural science foundations

• He has published more than 80 SCI papers in international authoritative magazines such as Alzheimer & dementia, Advanced Science, Brain, AJHG, etc.
  , and has been cited more than 600 times

• He has won 3 national invention patents and 6 provincial and ministerial scientific and technological achievement awards

• He was awarded the "Outstanding Young Talents Award of Chinese Research Hospitals", "China Outstanding Neurologist Young Physician Award", "Wuzhou Women's Science and Technology Award", "People's Famous Doctor - Excellent Style" and other honors

Expert reviews

With the advent of an aging society, AD has brought a heavy social and economic burden to the global public health system, the early identification of AD has become an urgent problem to be solved, and non-invasive, low-cost, hematology-based biological marker detection has become a popular research direction in recent ^years2
.

Foreign t-tau, NfL, Aβ42, Aβ40, tau181 and other detection indicators can not fully cover the AD markers, looking forward to the future of AD, we should explore more meaningful blood test indicators and detection technologies
.

• Aβ is shown to be a characteristic marker of the pathological process of AD, and the ratio of Aβ42/Aβ40 in peripheral plasma is more valuable in predicting the transition from normal people to MCI (mild cognitive impairment) or AD (AUC= 0.
77)²
.

• Overphosphorylation of tau protein is another typical pathological manifestation of
AD.

According to recent longitudinal data from a large prospective older cohort of the Alzheimer's Disease Neuroimaging Program (ADNI), P⁃tau181 reached abnormal levels in cerebrospinal fluid and 5.
7 years before Aβ abnormalities were found in cerebrospinal fluid and PET, suggesting that P⁃tau181 can be used as a novel diagnostic and screening tool
for the pre-dementia stage of AD.

P⁃tau181 is also a marker that can be used to monitor neurodegeneration and cognitive decline and is specific for ^AD2
.

• NfL is a marker of nerve axon injury and changes 10 years before clinical symptoms such as cognitive decline appear
.

Rapid increases in NfL levels in patients with MCI are associated with faster hippocampal atrophy, lower glucose metabolic rate, and faster overall cognitive ^{deterioration2}
.

• The results of the P⁃tau217 study show that it can distinguish AD from other neurodegenerative diseases, and the accuracy is significantly higher than that of MRI-based imaging biology markers
.

Elevated P⁃tau217 is associated
with deterioration of cognitive function and brain atrophy.

Therefore, plasma P⁃tau217 levels are expected to serve as biological markers for early AD ^pathology2
.

• In the future, multi-center studies are needed to determine the cut-off value of the AD blood marker in order to better serve the clinician's diagnosis
.

• In addition, because the AD biomarkers in the blood are mainly from the cerebrospinal fluid, these biomarkers usually drop significantly in concentration after crossing the blood-brain barrier into the blood, which significantly increases the difficulty of detection, so single-molecule immunoassay technology has emerged at home and abroad, and has been widely used in clinical research
.

Through the breakthrough of innovative single-molecule detection technology, the complexity of the detection technology path and the detection cost are significantly reduced, and the detection throughput, detection efficiency and detection stability
are improved.

In summary, the combination of multiple blood biomarkers is expected to become a noninvasive and effective method
for early identification of AD.

It is believed that with the rapid development of blood detection indicators such as P⁃tau181 and P-tau217 and single-molecule immune detection technology, the problem of early identification of AD will soon be solved, and the future can be expected
.