Scientists Develop Simple Blood Test for Early Detection of Alzheimer’s Disease

An international research team led by HKUST has developed a simple but robust blood test from Chinese patient data for early detection and screening of Alzheimer’s disease (AD) for the first time, with an accuracy level of over 96%.

Now, a team led by Prof. Nancy IP, Vice-President for Research and Development at HKUST, has identified 19 out of the 429 plasma proteins associated with AD to form a biomarker panel representative of an “AD signature” in the blood. Based on this panel, the team has developed a scoring system that distinguishes AD patients from healthy people with more than 96% accuracy. This system can also differentiate among the early, intermediate, and late stages of AD, and can be used to monitor the progression of the disease over time. These exciting findings have led to the development of a high-performance, blood-based test for AD, and may also pave the way to novel therapeutic treatments for the disease.

“With the advancement of ultrasensitive blood-based protein detection technology, we have developed a simple, noninvasive, and accurate diagnostic solution for AD, which will greatly facilitate population-scale screening and staging of the disease,” said Prof. Nancy Ip, Morningside Professor of Life Science and the Director of the State Key Laboratory of Molecular Neuroscience at HKUST.

The work was conducted in collaboration with researchers at University College London and clinicians in local hospitals including the Prince of Wales Hospital and Queen Elizabeth Hospital. The discovery was made using the proximity extension assay (PEA) – a cutting-edge ultrasensitive and high-throughput protein measurement technology, to examine the levels of over 1,000 proteins in the plasma of AD patients in Hong Kong.

As the most comprehensive study of blood proteins in AD patients to date, the work has recently been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, and has also been featured and actively discussed on different scholarly exchange platforms on AD research such as Alzforum.

AD, which affects over 50 million people worldwide, involves the dysfunction and loss of brain cells. Its symptoms include progressive memory loss as well as impaired movement, reasoning, and judgment. While patients often only seek medical attention and are diagnosed when they have memory problems, AD affects the brain at least 10-20 years before symptoms appear.

Source : The Hong Kong University of Science and Technology

New Blood Test Shows Great Promise in the Diagnosis of Alzheimer’s Disease

A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer’s disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer’s Association International Conference.

For many years, the diagnosis of Alzheimer’s has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer’s research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles—corresponding to the diagnosis of Alzheimer’s—in living people.

“The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer’s,” said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. “While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting.”

Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute’s Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer’s disease (ADAD)-causing mutation carriers and non-carriers from the world’s largest ADAD cohort.

  • In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of “intermediate or high likelihood Alzheimer’s” (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of “high likelihood Alzheimer’s” with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.
  • In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer’s and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.
  • In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

In each of these analyses, p-tau217 (a major component of Alzheimer’s disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer’s) and several other studied blood tests.

Other study leaders include Jeffrey Dage, PhD, from Eli Lilly and Company, who developed the p-tau217 assay, co-first authors Sebastian Palmqvist, MD, PhD, and Shorena Janelidz, PhD, from Lund University, and Eric Reiman, MD, Banner Alzheimer’s Institute, who organized the analysis of Arizona and Colombian cohort data.

In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer’s. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer’s. It has the potential to advance the disease’s research and care in other important ways.

“Blood tests like p-tau217 have the potential to revolutionize Alzheimer’s research, treatment and prevention trials, and clinical care,” said Eric Reiman, MD, Executive Director of Banner Alzheimer’s Institute in Phoenix and a senior author on the study. “While there’s more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years.”

Alzheimer’s is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.

Source: Lund University

Experimental Blood Test Detects Cancer up to Four Years before Symptoms Appear

Rachel Nuwer wrote . . . . . . . . .

For years scientists have sought to create the ultimate cancer-screening test—one that can reliably detect a malignancy early, before tumor cells spread and when treatments are more effective. A new method reported today in Nature Communications brings researchers a step closer to that goal. By using a blood test, the international team was able to diagnose cancer long before symptoms appeared in nearly all the people it tested who went on to develop cancer.

“What we showed is: up to four years before these people walk into the hospital, there are already signatures in their blood that show they have cancer,” says Kun Zhang, a bioengineer at the University of California, San Diego, and a co-author of the study. “That’s never been done before.”

Past efforts to develop blood tests for cancer typically involved researchers collecting blood samples from people already diagnosed with the disease. They would then see if they could accurately detect malignant cells in those samples, usually by looking at genetic mutations, DNA methylation (chemical alterations to DNA) or specific blood proteins. “The best you can prove is whether your method is as good at detecting cancer as existing methods,” Zhang says. “You can never prove it’s better.”

In contrast, Zhang and his colleagues began collecting samples from people before they had any signs that they had cancer. In 2007 the researchers began recruiting more than 123,000 healthy individuals in Taizhou, China, to undergo annual health checks—an effort that required building a specialized warehouse to store the more than 1.6 million samples they eventually accrued. Around 1,000 participants developed cancer over the next 10 years.

Zhang and his colleagues focused on developing a test for five of the most common types of cancer: stomach, esophageal, colorectal, lung and liver malignancies. The test they developed, called PanSeer, detects methylation patterns in which a chemical group is added to DNA to alter genetic activity. Past studies have shown that abnormal methylation can signal various types of cancer, including pancreatic and colon cancer.

The PanSeer test works by isolating DNA from a blood sample and measuring DNA methylation at 500 locations previously identified as having the greatest chance of signaling the presence of cancer. A machine-learning algorithm compiles the findings into a single score that indicates a person’s likelihood of having the disease. The researchers tested blood samples from 191 participants who eventually developed cancer, paired with the same number of matching healthy individuals. They were able to detect cancer up to four years before symptoms appeared with roughly 90 percent accuracy and a 5 percent false-positive rate.

The new study “offers several interesting approaches in the quest for a blood-plasma-based cancer-screening test,” says Colin Pritchard, a molecular pathologist at the University of Washington School of Medicine, who was not involved in the research. It will be important, though, for another research team to independently validate the findings in a different group of people before the test can be considered for clinical use, he says.

Usha Menon, a professor of gynecological cancer at University College London, who also did not participate in the study, observes that Zhang and his colleagues’ method provides a robust, preliminary baseline test—an “essential first step” toward a commercial cancer-screening product. “The authors are not suggesting that they have a test that can be used clinically at this stage,” she says. “They are clear that what they have is a robust preliminary demonstration of early detection of multiple cancer types four years prior to conventional diagnosis.”

Most likely, such a test would first target high-risk populations, Menon says. And it would require devising a second panel of tests to enable clinicians to determine the specific cancer type and rule out false positives.

Zhang believes such a feature could be developed with more work, and he agrees that further studies are needed. Given the challenges in repeating an effort of this magnitude, a government-industry partnership, he says, would ideally undertake the follow-up research. An ideal test would target the most common cancers, as Zhang’s study did, as well as the deadliest ones. “There are cancers where early detection can make a really big difference,” he says. Pancreatic cancer, for example, is the next target Zhang and his colleagues are working on.

If and when cancer blood tests do become available, Pritchard warns, they probably will not be able to detect all cancers before they become symptomatic. “One cancer might have a very long lead time, where another is very short,” he says. “Cancers that grow very quickly might not be detected even if someone is, for example, doing an annual screening.” It’s possible, too, that some types of malignancies may never be detected by blood tests because they do not produce a measurable signal in blood plasma.

“We are still a ways away from having an accurate blood-based ‘pan-cancer’ screening test. But it is not impossible to achieve,” Pritchard says. “There are several large efforts underway, with some promise for the future.”

Source: Scientific American


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Blood Tests Can Predict the Risk of Liver Cirrhosis

Repeated measurements of the biomarker FIB-4 in the blood every few years can predict the risk of developing severe liver disease, according to a new study from Karolinska Institutet published in the Journal of Hepatology. The risk of liver cirrhosis increases if the levels of this biomarker rise between two testing occasions.

Fat accumulation in the liver is common and is often seen in people with obesity or diabetes. In the worst case, fatty liver can lead to cirrhosis or liver cancer. It is unusual for this to occur but in those affected, symptoms often only occur at a late stage when there is no available treatment.

“It is difficult to predict the risk of cirrhosis, although you can get some guidance in using regular blood tests that measure liver damage,” says lead author Hannes Hagström, hepatologist at the Karolinska University Hospital and docent at Karolinska Institutet. “Therefore, we wanted to investigate whether what is known as the FIB-4 score can increase the accuracy of the identification of people at high risk, in particular with information from repeated measurements.”

Repeated sampling and measurements

The new study shows that repeated sampling and measurements of the FIB-4 score, rather than measuring FIB-4 on one sole occasion, can increase the prediction of future liver cirrhosis. The researchers used the AMORIS cohort that contains laboratory test data in a very large population, surveyed between 1985 and 1996. More than 40,000 people had blood test data for FIB-4 from several sampling occasions. They were followed in national registers to identify those who developed cirrhosis after up to 27 years.

The main finding was that the risk increases in people where the FIB-4 score rises between two testing occasions and decreases when it falls. In this way, almost half of those who were later affected by cirrhosis could be identified. One problem, however, was that the accuracy was relatively low, with a risk of false positive tests.

Long time to develop cirrhosis

The study also established that it took a long time to develop cirrhosis, and that it may be enough to recalculate the FIB-4 score at intervals of several years.

“We show that this biomarker is useful for identifying people in primary care with an increased risk of cirrhosis who may need to be more carefully investigated and to exclude people who do not need this,” says Dr Hagström. “But the method needs to be further developed to reduce the risk of false positive findings, which can lead to unnecessary examinations in healthy people.”

Source: Karolinska Institutet


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New Blood Test May Improve Liver Cancer Screening

An experimental blood test may improve screening for the most common form of liver cancer, researchers at the U.S. National Cancer Institute say.

The test checks people for previous exposure to certain viruses that may interact with the immune system and increase the risk of hepatocellular carcinoma (HCC), according to their new study.

“Together with existing screening tests, the new test could play an important role in screening people who are at risk for developing HCC. It could help doctors find and treat HCC early,” said study leader Xin Wei Wang, co-leader of the NCI Center for Cancer Research liver cancer program.

“The method is relatively simple and inexpensive, and it only requires a small blood sample,” he said in an institute news release.

Many screening tests detect features of cancer cells, but those features can change over time, and not all cancer cells in a tumor have the same characteristics, the authors noted. Rather than focus on cells, the new test detects features of the cancer’s environment — signs left behind by past viruses.

Infection with hepatitis B or hepatitis C virus, or cirrhosis of the liver are among the factors that increase the risk of HCC. It’s recommended that people with risk factors get screened for HCC every six months, undergoing an ultrasound with or without a blood test for alpha-fetoprotein.

If HCC is caught early, there’s a much better chance that it can be cured. But most patients are diagnosed when the cancer is advanced and often incurable.

“We need a better way to identify people who have the highest risk for HCC and who should get screened more frequently,” Wang said.

Improving early detection and monitoring of HCC are particularly important because HCC rates are rising in the United States.

The researchers are continuing to study their blood test and plan to assess it in clinical trials.

The study was published in the journal Cell.

Source: HealthDay


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