A new type of blood test can detect a hidden toxin behind Alzheimer's disease years before a patient shows any symptoms of memory loss or confusion. If the proof-of-concept can be further tested and scaled, the test could significantly speed up diagnosis, giving millions of patients answers and access to proper care long before their disease progresses. Researchers at the University of Washington (UW) created the novel blood test. It's designed to pick up on a molecular precursor in the blood that can cause proteins to irregularly fold and clump in the brain, ultimately forming amyloid beta (Aβ) plaques. Aβ plaques are a famous hallmark of Alzheimer's disease, but their role in cognitive decline is uncertain. Historically, these extracellular plaques have been considered an early trigger of neuron dysfunction and loss, ultimately leading to cognitive decline. But recent studies have shown that Aβ plaques are only present in a third of Alzheimer's patients, and sometimes, they are present in the brains of people who experience no cognitive deficits. In other words, extracellular Aβ plaques in the brain aren't necessarily toxic in and of themselves, but they might stem from notoriously difficult-to-detect molecular toxins. These toxins are essentially the functional versions of the Aβ found within cells. They are known as 'toxic Aβ oligomers', and some scientists think they could subtly damage neurons from afar, somehow predisposing the cells to extracellular plaques and clumps. Scientists are still figuring out the details, but the hypothesis has led UW researchers to make an impressively accurate soluble oligomer binding assay, nicknamed SOBA. Researchers first tested SOBA on 310 participants' blood plasma. Some participants showed mild cognitive impairment or Alzheimer's disease, while others were in good cognitive health. By measuring toxic Aβ oligomers in the blood plasma, SOBA picked out all 53 participants with Alzheimer's who were later confirmed to have the disease post-mortem. Meanwhile, in the control group, SOBA detected oligomers in the blood plasma samples of 11 individuals. Ten of these participants were later diagnosed with mild cognitive impairment or Alzheimer's. "What clinicians and researchers have wanted is a reliable diagnostic test for Alzheimer's disease – and not just an assay that confirms a diagnosis of Alzheimer's, but one that can also detect signs of the disease before cognitive impairment happens," says bioengineer Valerie Daggett from UW. "That's important for individuals' health and for all the research into how toxic oligomers of amyloid beta go on and cause the damage that they do. What we show here is that SOBA may be the basis of such a test." And that's not all SOBA can do. After all, Alzheimer's isn't the only disease marked by toxic oligomers. Misfolding proteins also seem to be associated with Parkinson's disease, type II diabetes, and Lewy body dementia, which means SOBA could one day be tweaked to pick up early markers of these other illnesses. Other tests have also attempted to measure for markers of Alzheimer's, but with varying levels of success. In 2018, for example, a blood analysis that also detects Aβ precursors predicted the onset of Alzheimer's up to 30 years before the cognitive deficits even began to show. SOBA, researchers say, can make similar predictions. In current clinical practice, only blood tests that measure for genes associated with Alzheimer's are in use, but these tests are not as good at predicting who will go on to actually develop the disease. With tests like SOBA performing so well, that could be on the brink of changing. Source
