A New Blood Test Detects Alzheimer’s Dementia with 93 percent Accuracy

A blood test developed at Washington University School of Medicine in St. Louis has proven highly accurate in detecting early signs of Alzheimer’s disease in a study involving nearly 500 patients from across three continents, providing further evidence that the test should be considered for routine screening and diagnosis.

Our study shows that the blood test provides a robust measure for detecting amyloid plaques associated with Alzheimer’s disease, even among patients not yet experiencing cognitive declines,” said senior author Randall J. Bateman, MD,  Professor of Neurology. “A blood test for Alzheimer’s provides a huge boost for Alzheimer’s research and diagnosis, drastically cutting the time and cost of identifying patients for clinical trials and spurring the development of new treatment options,” Bateman said. “As new drugs become available, a blood test could determine who might benefit from treatment, including those at very early stages of the disease.”

Developed by Bateman and colleagues, the blood test assesses whether amyloid plaques have begun accumulating in the brain based on the ratio of the levels of the amyloid beta proteins Aβ42 and Aβ40 in the blood.

Researchers have long pursued a low-cost, easily accessible blood test for Alzheimer’s as an alternative to the expensive brain scans and invasive spinal taps now used to assess the presence and progression of the disease within the brain.

Evaluating the disease using PET brain scans – still the gold standard – requires a radioactive brain scan, at an average cost of $5,000 to $8,000 per scan. Another common test, which analyzes levels of amyloid-beta and tau protein in cerebrospinal fluid, costs about $1,000 but requires a spinal tap process that some patients may be unwilling to endure.

This study estimates that prescreening with a $500 blood test could reduce by half both the cost and the time it takes to enroll patients in clinical trials that use PET scans. Screening with blood tests alone could be completed in less than six months and cut costs by tenfold or more, the study finds.

Source: https://medicine.wustl.edu/

NeuroInflammation Critical in the Developement of Alzheimer’s

Doctors regard amyloid plaque lodged between the brain’s nerve cells and tangled tau protein fibers forming within the cells as the hallmark of Alzheimer’s disease. However, amyloid plaque — consisting of broken pieces of protein that clump together — is also present in the brains of older adults who do not develop Alzheimer’s, suggesting another factor is triggering the disease.

A new study finds that inflammation in the brain drives the progression from the presence of amyloid plaque and tau tangles to the onset of dementia and Alzheimer’s disease.
Lead author of the study, Dr. Tharick Pascoal, Ph.D., assistant professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, PA, explains:

Many [older adults] have amyloid plaques in their brains but never progress to developing Alzheimer’s disease. We know that amyloid accumulation on its own is not enough to cause dementia — our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to widespread brain damage and cognitive impairment.”

While scientists have observed neuroinflammation in people with Alzheimer’s before, the new study reveals for the first time its critical role in the development of the disease. The research finds that activating the brain’s immune cells — its microglial cellspromotes the spread of tangled tau proteins that comprise amyloid plaque.

Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of medical and scientific relations, who was not involved in the study, explained the purpose of neuroinflammation to Medical News Today. The Alzheimer’s Association contributed funding to the research.

Inflammation has an important role in fighting off infection and other pathogens in the body, including in the brain and central nervous system,” said Snyder. Microglia “help clear debris (damaged neurons, infections) from the brain.” “However,” adds Dr. Snyder, “a sustained inflammatory response, or a change from acute to chronic neuroinflammation, may contribute to the underlying biology of several neurodegenerative disorders.

Inflammation is not by itself associated with cognitive impairment, daid Dr. Pascoal. “However when neuroinflammation converges with amyloid pathology, the interaction potentiates tau pathology. As a consequence, the coexistence of these three processes in the brain — amyloid, neuroinflammation, and tau pathology — determines cognitive deterioration.”

Results suggest that the combination of anti-amyloid with anti-inflammatory therapies in the early stages of the disease, when the pathology of tau is still confined to the temporal cortex, would maximize the efficacy of these drugs.”

The study appears in Nature Medicine.

Source: https://www.medicalnewstoday.com/

Simple Diagnostic Tool Predicts Individual Risk of Alzheimer’s

Researchers at Lund University in Sweden have developed an algorithm that combines data from a simple blood test and brief memory tests, to predict with great accuracy who will develop Alzheimer’s disease in the future.

Approximately 20-30% of patients with Alzheimer’s disease are wrongly diagnosed within specialist healthcare, and diagnostic work-up is even more difficult in primary care. Accuracy can be significantly improved by measuring the proteins tau and beta-amyloid via a spinal fluid sample, or PET scan. However, those methods are expensive and only available at a relatively few specialized memory clinics worldwide. Early and accurate diagnosis of AD is becoming even more important, as new drugs that slow down the progression of the disease will hopefully soon become available.

A research group led by Professor Oskar Hansson at Lund University have now shown that a combination of relatively easily acccessible tests can be used for early and reliable diagnosis of Alzheimer’s disease. The study examined 340 patients with mild memory impairment in the Swedish BioFINDER Study, and the results were confirmed in a North American study of 543 people.

A combination of a simple blood test (measuring a variant of the tau protein and a risk gene for Alzheimer’s) and three brief cognitive tests that only take 10 minutes to complete, predicted with over 90% certainty which patients would develop Alzheimer’s dementia within four years. This simple prognostic algorithm was significantly more accurate than the clinical predictions by the dementia experts who examined the patients, but did not have access to expensive spinal fluid testing or PET scans, said Oskar Hansson.

Our algorithm is based on a blood analysis of phosphylated tau and a risk gene for Alzheimer’s, combined with testing of memory and executive function. We have now developed a prototype online tool to estimate the individual risk of a person with mild memory complaints developing Alzheimer’s dementia within four years”, explains Sebastian Palmqvist, first author of the study and associate professor at Lund University.

One clear advantage of the algorithm is that it has been developed for use in clinics without access to advanced diagnostic instruments. In the future, the algorithm might therefore make a major difference in the diagnosis of Alzheimer’s within primary healthcare.

The algorithm has currently only been tested on patients who have been examined in memory clinics. Our hope is that it will also be validated for use in primary healthcare as well as in developing countries with limited resources”, says Sebastian Palmqvist.

Simple diagnostic tools for Alzheimer’s could also improve the development of drugs, as it is difficult to recruit the suitable study partcipants for drug trials in a time- and cost-effective manner. ”The algorithm will enable us to recruit people with Alzheimer’s at an early stage, which is when new drugs have a better chance of slowing the course of the disease”, concludes Professor Oskar Hansson.

The findings are published in Nature Medicine.

Source: https://www.lunduniversity.lu.se/

Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/