Massive blood sampling study identifies predictors of Alzheimer’s risk


While the exact causes behind Alzheimer’s are still unknown, research is beginning to demonstrate how biomarkers of the disease might reveal themselves long before symptoms appear, raising the prospect of earlier diagnosis and better treatments for patients. A new study, claimed to be the most comprehensive of its type, has demonstrated how concentrations of certain proteins in the blood might indicate the onset of the condition far in advance, and has pinpointed one that may even help trigger it.

From sniff tests to blood tests to eye examinations, scientists are exploring many possibilities in the search for early diagnostic tools for Alzheimer’s, and with very good reason. As there is no way to treat or reverse the cognitive decline associated with the disease, the best opportunity to tackle it may well be before these symptoms start to appear. By pursuing these types of technologies, researchers may be able to pick up signs of the Alzheimer’s years or even decades in advance.

Of these possibilities, blood sampling shapes as a particularly promising one. We’ve seen a number of early studies demonstrate high degrees of accuracy when it comes to this diagnostic technique, by scanning the blood for proteins called tau and amyloid that are thought to drive the formation of toxic brain plaques and tangles linked to the disease.

The new study conducted by researchers at Johns Hopkins University expands the scope of this in a big way. The scientists started by analyzing historical blood samples of more than 4,800 middle-aged and elderly subjects collected around a decade ago, identifying almost 5,000 distinctive proteins in their plasma. Abnormal levels of 38 of these proteins were found to be “significantly associated” with a higher risk of developing Alzheimer’s in the five years after the sample was collected.

Next, the researchers measured protein levels in blood samples taken from more than 11,000 younger subjects, collected between 1993 to 1995. Abnormal levels of 16 of the same 38 proteins were associated with the development of Alzheimer’s nearly two decades later, at follow-up clinical evaluations between 2011 and 2013. A separate review of blood samples on Icelandic subjects involving some of these proteins verified these findings, finding six of them were again associated with heightened Alzheimer’s risk around a decade later.

The study may have uncovered more than just blood-based biomarkers that appear to correlate with Alzheimer’s risk. The scientists also compared this group of proteins with past research into genetic links to Alzheimer’s, which revealed strong evidence that one of them, called SVEP1, may actually be involved in triggering the disease. The protein was found to be part of larger protein networks associated with dementia, while circulating levels were linked with atrophy in parts of the brain susceptible to Alzheimer’s pathology.

“This is the most comprehensive analysis of its kind to date, and it sheds light on multiple biological pathways that are connected to Alzheimer’s,” says study senior author Josef Coresh. “Some of these proteins we uncovered are just indicators that disease might occur, but a subset may be causally relevant, which is exciting because it raises the possibility of targeting these proteins with future treatments.”

From here, the scientists hope to build on these findings by further analyzing proteins in blood samples collected during long-term studies to unearth more potential triggers for Alzheimer’s that could be targets for new treatments.

The research was published in the journal Nature Aging.

Source: Johns Hopkins University





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