Is a blood test reliable for detecting Alzheimer's disease?
China News Weekly reporter/Niu He
Published in the 1131st issue of "China News Weekly" magazine on March 11, 2024
By going to the hospital and drawing less than 5 microliters of blood, it is possible to screen for Alzheimer's disease in advance.
Recently, the official website of the Hong Kong University of Science and Technology (hereinafter referred to as "HKUST") announced that the research team of Ip Yu-ru, the president of the school, Professor of Life Sciences at Morningside and Director of the Hong Kong Center for Neurodegenerative Diseases, has developed a blood test that can detect early Detect Alzheimer's disease and mild cognitive impairment with an accuracy of over 96% and 87% respectively.
Alzheimer's disease is the main type of dementia.
Currently, cerebrospinal fluid detection and PET-CT combined with protein tracers are the gold standard for diagnosing Alzheimer's disease. The former extracts a certain amount of cerebrospinal fluid from the spinal gap through lumbar puncture; the latter injects radioactive protein tracers into the body. tracer, detecting pathogenic proteins through imaging means.
Multiple interviewees told China News Weekly that these two detection methods are not widely used in clinical applications due to their invasiveness and high price.
In contrast, blood testing is more convenient and faster, and has become a hot topic in the field of Alzheimer's disease diagnosis and research in recent years.
Since the beginning of this year, in addition to the research by HKUST, a number of related studies at home and abroad have been released.
Peiminder Sachdev, professor of neuropsychiatry at the University of New South Wales in Sydney and co-director of the Australian Dementia Network, told China News Weekly that overall, blood testing for early Alzheimer's disease is still in the research stage. The study needs to be repeated to obtain more information.
Blood tests become a new trend
In the latest research from the Hong Kong University of Science and Technology, early detection of Alzheimer's disease can be achieved by analyzing the levels of 21 protein biomarkers (hereinafter referred to as "markers") in plasma samples.
Ye Yuru said that the detection method is simple, efficient and low-invasive, and can be used to screen suitable patients for clinical trials and drug treatment, as well as monitor disease progression and drug response.
"This research is an extension of the 2021 research." Jiang Yuanbing, a postdoctoral researcher at the Hong Kong University of Science and Technology, said in an interview with China News Weekly.
Jiang Yuanbing is a member of Ye Yuru's team and the first author of this latest study from HKUST.
The study recruited three groups of people consecutively, including more than 1,000 Hong Kong participants and 217 Spanish participants.
The first group of 1,000 Hong Kong subjects were diagnosed with Alzheimer's disease and mild cognitive impairment based on clinical symptom judgment and magnetic resonance imaging.
The other two groups of subjects had clear pathological evidence and underwent PET-CT and cerebrospinal fluid testing respectively.
In 2021, Ye Yuru's team published a study in an authoritative international journal, collecting plasma samples from Hong Kong Alzheimer's disease patients and detecting changes in the levels of more than 1,000 proteins.
In the end, the research team identified 19 marker groups characteristic of the disease from 429 plasma proteins related to Alzheimer's disease, and then designed a scoring system that can classify Alzheimer's disease patients from It can be distinguished among healthy people with an accuracy of over 96%.
The system can also identify early, middle and late stages of Alzheimer's disease and can be used to monitor the progression of the patient's disease.
Jiang Yuanbing said that through research in 2021, the team theoretically proposed a prototype of blood detection technology.
This year's study selected and integrated 21 key markers discovered in previous studies to develop current blood diagnostic technology for actual testing.
These 21 markers, in addition to the 19 markers in previous studies, also include some other markers.
Different from 2021, this study has included domestic and European populations recruited in Hong Kong, confirming that this blood testing technology can be used for people in different countries.
In the research field of Alzheimer's disease blood testing, Jiang Yuanbing's team has been following up for seven or eight years.
Jiang Yuanbing said that initially, blood testing was not recognized by everyone.
When the team first decided to do research in this area, many people around them, including some team members, were skeptical.
"Alzheimer's disease is a brain-related disease, and there was very little research on this area at the time. When the research team initially collected blood samples from patients, people who didn't understand thought it was a waste of time," he said.
The specific cause of Alzheimer's disease is not yet fully understood. The main pathophysiological changes in the brain of patients with this disease include neurofibrillary tangles caused by beta-amyloid deposition in the brain and hyperphosphorylation of tau protein, leading to neuronal and Connection loss etc.
Sun Yong'an, chief physician of the Department of Neurology at Peking University First Hospital, told China News Weekly, "The currently internationally recognized markers for blood detection of Alzheimer's disease include Aβ42/40, p-tau181, p-tau217, etc. In addition, , Glial fibrillary acidic protein (English abbreviation GFAP) is also very helpful in disease diagnosis."
In January 2018, researchers from the National Center for Geriatrics in Japan published a study in Nature that took the lead in reversing doubts.
The research team developed a new blood test method to predict Alzheimer's disease through peripheral blood samples (blood other than bone marrow). The accuracy of this technology is more than 90%.
The study also demonstrates the potential clinical use of markers in predicting levels of beta-amyloid deposits in an individual's brain.
"This research was a milestone and caused great controversy in the academic community at the time. Many people did not believe that blood testing could be used as an auxiliary diagnosis method. Later, after some results were achieved in this field at home and abroad, everyone finally This method is beginning to be gradually recognized,” said Jiang Yuanbing.
This year, there have been constant new developments in the field of Alzheimer's disease blood testing.
In a study published in the Journal of the American Medical Association Neurology on January 22, researchers at the University of Gothenburg in Sweden developed a blood test based on the p-tau217 protein.
The study analyzed data from three different trials in the United States, Canada and Spain, involving 786 people, including people with and without cognitive impairment.
In all three trials, patients underwent either a lumbar puncture or an amyloid PET scan.
It was found that the blood test was able to identify relevant abnormalities with "high accuracy" and was comparable to the accuracy of cerebrospinal fluid tests.
In a study published in Nature Aging on February 12, the team of Yu Jintai, chief physician of the Department of Neurology, Huashan Hospital Affiliated to Fudan University, analyzed the blood data of more than 50,000 patients on more than 1,460 plasma protein data. It was found that elevated levels of three markers, including GFAP, are associated with Alzheimer's disease.
Levels of these proteins in the blood of participants with dementia were outside the normal range more than a decade before symptoms appeared.
Among them, people with higher GFAP levels are 2.32 times more likely to develop dementia in the future than those with lower GFAP levels.
Yu Jintai told China News Weekly that in a study published by his team last year, the subjects were patients with Alzheimer's disease, and the diagnosis was made through cerebrospinal fluid testing and PET scanning.
Based on the blood test for the GFAP marker developed by the team, the accuracy of subjects' diagnosis of Alzheimer's disease was 97%, and the accuracy of diagnosing early asymptomatic Alzheimer's disease was 89%.
Sachdev told China News Weekly that the development of Alzheimer's disease blood testing technology is exciting.
He said that p-tau217 is one of the most promising markers in blood.
Although GFAP is not a specific marker for Alzheimer's disease, it is also a good marker of brain degeneration and can help support the clinical diagnosis of dementia caused by any cause.
Yu Jintai analyzed that Alzheimer's disease has an insidious onset in the early stages. In the past, when patients were diagnosed, they were usually already in the middle and late stages. This type of blood test is of great significance in the diagnosis of early Alzheimer's disease.
Sun Yongan said that for patients with Alzheimer's disease, the purpose of early diagnosis is early intervention.
The earlier the disease is detected and scientific prevention and treatment are carried out, the more obvious the course of the disease will be delayed and the greater the benefit will be for the patient.
In late-stage patients, many nerve cells in the brain have died. The number of neurons in the brain is limited and cannot be regenerated, so the therapeutic effect is greatly reduced.
In the existing clinical research on Alzheimer's disease drugs, the subjects included in the clinical trials are basically patients with early-stage Alzheimer's disease and patients with mild cognitive impairment.
Wang Jun, president of the Alzheimer's Disease Prevention and Treatment Association, mentioned in September 2021 that early assessment, early detection, and early intervention can reduce the incidence of Alzheimer's disease by 30%, delay the onset by 5 years, and reduce the incidence rate by 50%.
In July last year, at the 2023 Alzheimer's Disease Association International Conference, a new revised draft of the Alzheimer's disease diagnostic criteria was announced, which included plasma biomarkers in biomarker classification, disease diagnosis and staging.
Blood tests cannot 100% rule out Alzheimer's disease.
"The core of Alzheimer's disease blood testing is to assist doctors in clinical diagnosis and replace some of the clinical needs for PET scans or cerebrospinal fluid testing. In the future, the team will develop blood testing technology suitable for large-scale population screening." Jiang Yuanbing said, The lesions of patients with Alzheimer's disease not only involve the nervous system. Blood tests based on 21 markers can simultaneously assess changes in markers involving neurodegenerative changes, vascular function, and metabolic activity, which can help distinguish different causes. For patients with unknown causes, future treatment can be more targeted.
There is still a lack of standardized processes
In September 2022, Wang Haidong, director of the Department of Aging of the National Health Commission, said that there are about 15 million dementia patients in China among the elderly aged 60 and above, 10 million of whom are Alzheimer's disease patients.
Sun Yongan said that because of the intensification of the aging problem in China, the market prospect of blood testing for Alzheimer's disease is broad.
According to reports, in July last year, the blood testing technology developed by Ye Yuru’s team entered the Hong Kong market, with the price of each test being about 7,000 yuan.
The team recommends that the test be used by people who have a family history of Alzheimer's disease or who are over 50 and experience memory loss.
The research team has licensed the technology to a start-up company and is working with doctors from a number of private hospitals in Hong Kong to provide blood testing services to the public.
"We are also trying to push into the inland now." Jiang Yuanbing said.
"Each laboratory has different blood testing methods. In the end, which one is more effective depends on the market." Yu Jintai said that Alzheimer's disease blood samples and related technologies are already available, and the markers are also very clear. Now as long as there are relevant policies and capital willing to promote it, it can be launched into the market soon.
Yu Jintai said that the researchers of the team are in commercialization negotiations with some companies, and it is expected that the GFAP-based blood testing technology will be applied to clinical testing in half a year.
Yu Jintai said that domestic physical examination medical institutions have contacted his team to discuss adding relevant tests to the physical examination items.
Abroad, Alzheimer's disease blood testing is progressing faster.
In October 2019, Susan Schindler, a dementia expert at Washington University School of Medicine in St. Louis, and her colleagues published a study in the journal Neurology and found that amyloid plaques can be detected through blood tests. attracted industry attention.
Schindler told China News Weekly that this test has been commercialized in the United States to identify those who have normal cognition but are at risk of Alzheimer's disease in the brain.
Today, Schindler's lab offers more than 10 blood tests for Alzheimer's disease, National Public Radio reported in January.
"In clinical practice, it is very important to use highly accurate blood tests." Schindler said that the accuracy of Alzheimer's disease blood tests currently available in the United States varies, ranging from about 70% to 95%. wait.
A chief physician in the neurology department of a domestic tertiary hospital told China News Weekly that as far as he knew, in the field of Alzheimer's disease diagnosis, domestic companies had introduced corresponding blood testing products to the clinic more than ten years ago, but The actual effect is not ideal, and in clinical practice, the accuracy of this type of product is not high.
Sun Yongan said that only a few hospitals in mainland China have small-scale clinical applications of Alzheimer's disease blood testing.
Yu Jintai said that domestic laboratory testing processes lack unified and standardized operating procedures.
Each laboratory will produce different results based on different markers.
Sun Yongan said that the blood test results for the same Alzheimer's disease in different laboratories vary greatly. These differences depend on various detailed factors such as the amount of blood sampled, the sample storage method and the freezing time.
Take the Aβ42/40 marker as an example. Some test tubes have adsorption properties for this marker.
"The Aβ42/40 content in blood is originally low. If the test tube is slightly adsorbed, the test results will be very different. After the blood sample is put into the test tube, it has to go through steps such as packaging and freezing. The materials of the divided test tubes are different and the freezing time is different. , will also lead to different results." He said.
In Yu Jintai's view, whether peripheral blood testing can become the gold standard for Alzheimer's disease diagnosis depends on whether the test can have a standardized process, rather than changing the operation method and the results will change.
"Blood is easily degraded and attached to foreign objects, and is greatly affected by the external environment." He said.
In addition to the lack of unified standards, Sachdev analyzed that the health data of Alzheimer's disease patients in existing relevant studies are not clear, and the patient's kidney function, liver function, medication status, etc. will affect the measurement results; Alzheimer's disease It is not clear at what stage of silent disease progression will abnormal blood tests appear; it is also uncertain whether the disease will definitely progress in patients who are selected very early.
He believes that even if the Alzheimer's disease blood test is highly accurate, if the method is rolled out on a large scale, a large number of false positives will be obtained, which will lead to the problem of over-testing.
In the future, these tests will play a role in screening individuals as drugs to treat Alzheimer's disease become more widely available.
In reality, people’s awareness of proactive screening is not high.
The "Survey Report on the Current Awareness and Demand for Alzheimer's Disease in China" released in September 2022 shows that the total awareness rate of Alzheimer's disease among the domestic population exceeds 90%, but the willingness to actively seek medical treatment is only more than 10%.
Yu Jintai said that his hospital currently has a high rate of early diagnosis of Alzheimer's disease in the country. According to his estimate, the current early diagnosis rate of Alzheimer's disease in his hospital does not exceed 10%.
Sun Yong'an said that his hospital has tried to screen for Alzheimer's disease through blood testing for scientific research.
Last year, his department was equipped with a fully automatic blood testing equipment that can detect more than a dozen markers at the same time, but in terms of stability, it is still being explored and debugged.
In Sun Yongan's view, whether the standards for blood testing can be unified in the future depends on whether one or two markers can be found among many markers that are very stable, have high reproducibility of results, and have low detection costs.
In Jiang Yuanbing's view, Alzheimer's disease blood testing is now "letting a hundred flowers bloom", and the methods proposed by various research teams should eventually be gradually unified.
The clinical use of this method still faces challenges, such as how to integrate or replace existing diagnostic methods.
"In the next two to three years, I believe that blood testing will be applied in small-scale clinical applications, and will be gradually rolled out under the premise of relatively good clinical effects. In the process from small-scale application to large-scale rollout, more from Verification and optimization of all parties to better meet actual clinical needs," he said.
In August last year, US independent medical laboratory giant Quest launched the first direct-to-consumer blood test product to detect abnormal values of beta amyloid protein.
The testing product is worth US$399, approximately 2,900 yuan, and adults over 18 years old in the United States can purchase it online.
Sachdev believes that Alzheimer's blood tests can only be used by dementia specialists in specialist hospitals and are not available directly to consumers.
"The use of this test product in home and community settings is not recommended and can cause unnecessary anxiety," he said.
"China News Weekly" Issue 9, 2024
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