Tag: biomarker

Categories : Lab Tests and Imaging Neurodegenerative DiseasesTags :

Could a Blood Test Rule out Future Dementia Risk?

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Researchers at Karolinska Institutet have demonstrated how specific biomarkers in the blood can predict the development of dementia up to 10 years before diagnosis with high accuracy, among older adults living independently in the community.

A new study, published in Nature Medicine, has investigated the potential of specific biomarkers such as tau217, Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP) to predict the occurrence of dementia, including Alzheimer’s disease, up to ten years before an actual diagnosis in cognitively healthy older adults living in the community. 

Blood samples from more than two thousand

Previous research has suggested that these biomarkers could be useful in early dementia diagnostics, but most studies involved individuals who have already sought medical care for cognitive issues, due to cognitive concerns or cognitive symptoms, such as memory difficulties. 

A larger, community-based study, was necessary to determine the predictive value of biomarkers in the general population.

Led by researchers from the Aging Research Center of Karolinska Institutet in collaboration with SciLifeLab and KTH Royal Institute of Technology in Stockholm, the study analysed blood biomarkers in more than 2100 adults aged 60+, who were followed over time to determine if they developed dementia.

At a follow-up ten years later, 17% of participants had developed dementia. The accuracy of the biomarkers used in the study was found to be up to 83%.

“This is an encouraging result, especially considering the 10-year predictive window between testing and diagnosis. It shows that it is possible to reliably identify individuals who develop dementia and those who will remain healthy,” says Giulia Grande, assistant professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and first author of the study.

Promising biomarkers

“Our findings imply that if an individual has low levels of these biomarkers, their risk of developing dementia over the next decade is minimal”, explains Davide Vetrano, associate professor at the same department and the study’s senior author. “This information could offer reassurance to individuals worried about their cognitive health, as it potentially rules out the future development of dementia.”

However, the researchers also observed that these biomarkers had low positive predictive values, meaning elevated biomarker levels alone could not reliably identify individuals who would surely develop dementia within the next ten years. Therefore, the study authors advise against widespread use of these biomarkers as screening tools in the population at this stage.

“These biomarkers are promising, but they are currently not suitable as standalone screening tests to identify dementia risk in the general population,” says Davide Vetrano. 

The researchers also noted that a combination of the three most relevant biomarkers – p-tau217 with NfL or GFAP – could improve predictive accuracy.

“Further research is needed to determine how these biomarkers can be effectively used in real-world settings, especially for elderly living in the community or in primary health care services,” says Grande.

“We need to move a step further and see whether the combination of these biomarkers with other clinical, biological or functional information could improve the possibility of these biomarkers to be used as screening tools for the general population”, Grande continues.

The study was mainly funded by the Swedish Research Council, The Swedish Brain Foundation and The Strategic Research Area in Epidemiology and Biostatistics at Karolinska Institutet. The researchers declare that there are no conflicts of interest.

Source: Karolinska Institutet

Categories : NeurologyTags :

Review Re-evaluates Biomarker for Imaging Neuroinflammation

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Neuroinflammation can lead to serious neurological or psychiatric diseases, for which there is presently one biomarker available for medical imaging to visualise cerebral inflammation. Trouble is, it has been unclear how to interpret this biomarker. Researchers have now found that a large quantity of this protein indicates a large quantity of inflammatory cells, but its presence is not a sign of their overactivation. These results, published in Nature Communications, pave the way for optimal observation of neuroinflammatory processes with other potential biomarkers, and a re-evaluation of prior research.

In the brain, microglial cells play an important role in inflammation and its potential overactivation. They can be ”activated” when dysfunction occurs, phagocytise pathological cells or proteins and even produce protective substances. Currently, in medical imaging, only one marker can be used to locate and measure microglia non-invasively and in vivo: the TSPO protein, which is present in these cells. This protein can be observed by Positron Emission Tomography (PET), a common imaging technique.

A TSPO of insight

”Hundreds of studies have used PET scans of this protein to explore and quantify microglia. However, no study has succeeded in precisely interpreting the significance of its quantity in the context of an inflammatory reaction,” explains Stergios Tsartsalis, senior clinical associate in the Department of Psychiatry at the UNIGE Faculty of Medicine. Together with other researchers, Stergios Tsartsalis sought to determine if a large quantity of TSPO correspond to a large quantity of inflammatory cells, and whether it is a sign of their overactivation.

The international research team worked on the brains of mouse models of Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis, and on post-mortem brain samples from patients affected by the same diseases. ”We discovered that a high density of TSPO protein is indeed an indicator of a high density of microglia. On the other hand, the observation of TSPO does not allow us to say whether or not the inflammatory cells are overactivated,” explains the UNIGE researcher, co-first author of the study.

Re-reading the past, optimising the future

This discovery highlights the value of medical imaging of TSPO: it makes it possible to identify cases where the neuroinflammatory disease is linked to a deregulation in the number of glial cells. In addition, the scientists have identified two markers of the state of microglia activation in humans – the LCP2 and TFEC proteins – setting the stage for new medical imaging approaches.

”These results represent a further step towards understanding the role of microglia in neuroinflammation. They will help to optimise the focus of future studies and also to review the conclusions of previous research,” enthuses Stergios Tsartsalis.

Source: Université de Genève

Categories : Ageing Injury & TraumaTags :

A Biomarker for Male Hip Fracture Risk

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Photo by Mehmet Turgut Kirkgoz on Unsplash

In new research published in the Journal of Bone and Mineral Research, elevated blood levels of a certain chemokine, or small signalling protein, that promotes osteoclast formation were linked with a higher risk of hip fracture in men.

To maintain bone health, a balanced activity of various bone cell types including bone-forming osteoblasts and bone-resorbing osteoclasts has to take place. When osteoclasts dominate without adequate bone formation to compensate, osteoporosis results.

The study included 55 men and 119 women who had experienced a hip fracture an average of 6.3 years after their blood was collected. The participants were matched individually to controls who did not develop hip fractures.

The researchers found higher levels of the chemokine CXCL9 in the pre-fracture blood samples of men with subsequent hip fractures compared with their non-fracture controls. In women, the researchers saw no such.

“The unexpected difference in the results between men and women in our study may be explained by how changes in sex hormone levels during aging could influence the level and effects of CXCL9 differently in older men and women,” explained corresponding author Woon-Puay Koh, MBBS, PhD, from the National University of Singapore (NUS).

“Our findings open the exciting possibility that early interventions targeting CXCL9 or CXCL9-CXCR3 signalling could be beneficial in preventing hip fractures in older men,” added co-corresponding author Christoph Winkler, PhD, also from NUS.

Source: Wiley

Categories : Cardiovascular DiseaseTags :

New Easy Biomarker for Cardiovascular Risk

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Image by Landon Arnold on Unsplash

A large study has shown that apolipoproteins apoB and apoA-1 together provide early and reliable cardiovascular risk information as well as levels of low-density lipoprotein (LDL) cholesterol. The researchers advocate introducing new guidelines for detecting cardiac risk and say the results, published in PLOS Medicine, may pave the way for early treatment, which could help lower morbidity and mortality rates.

Cardiovascular disease is the most common cause of death globally and includes a wide range of conditions, such as stroke and myocardial infarction with atherosclerosis in different organs of the body. In many cases the disease can be prevented and arrested with lifestyle changes and lipid-lowering treatments using statins and other methods.

The cardiac risk assessment usually uses reference values for the LDL cholesterol. Other types of fat particles can also be measured along with apolipoproteins, which transport cholesterol in the blood. International guidelines for cardiovascular disease recommend using apolipoprotein apoB, which transports LDL cholesterol, as an alternative risk marker for people with type 2 diabetes, overweight and very high levels of blood lipids.

Recent research has, however, indicated the importance of also factoring in the apolipoprotein apoA-1, which transports the protective and anti-inflammatory HDL cholesterol. Calculating the apoB/apoA-1 ratio gives a risk quotient reflecting the balance between the fat particles that expedite atherosclerosis and the “good” protective apoA-1 particles that arrest the process.

In this present study, the researchers have analysed the link between cardiovascular disease and apoB/apoA-1 values in more than 137 000 Swedish adults between the ages of 25 and 84. The individuals were followed for 30 years, during which time 22 000 suffered some form of cardiovascular event. The analysis methods are simple, inexpensive and safe, and do not require pre-test fasting, as is the case with LDL and non-HDL tests. Basing their study on a large database, the researchers linked the laboratory analyses to several clinical diagnosis registers.

“The results show that the higher the apoB/apoA-1 value, the greater the risk of myocardial infarction, stroke and need for coronary surgery,” says Göran Walldius, senior author and professor emeritus at the Institute of Environmental Medicine, Unit of Epidemiology, Karolinska Institutet. “The study also showed that the risk was amplified in the presence of low protective levels of apoA-1.”

Individuals with the highest apoB/apoA-1 values had a 70% higher risk of severe cardiovascular disease and almost triple the risk of non-fatal myocardial infarction compared with those with the lowest apoB/apoA-1 values. Individuals with the highest risk quotient were also more affected by severe cardiovascular diseases many years earlier than individuals with the lowest apoB/apoA-1 values.

The relationship was observed in both men and women and the elevated levels could be detected as early as 20 years before the onset of cardiovascular disease.

“Early preventive treatment and information about cardiovascular risk is, of course, important in enabling individuals to manage their risk situation,” Walldius says. “Early treatment can also reduce the cost burden on the public health services.”

Taken together, the results suggest that the apoB/apoA-1 ratio is a better marker for identifying at-risk individuals for cardiovascular disease compared to the apoB method alone.

“It should be possible to introduce cut-values for apoB, apoA-1 and the apoB/apoA-1 ratio into new guidelines as a complement to current guidance on the detection and treatment of dyslipidaemia,” said Walldius.

Source: Karolinska Institutet