Faulty genes might lead to changes in urine that appear early on in Alzheimer’s disease, a new study has found. Although only demonstrated in rodents, if the same holds true for humans, scientists might be able to use these alterations as a way to improve disease detection, a welcomed outcome in the face of today’s growing epidemic.
At present, Alzheimer’s diagnoses often come when obvious mental symptoms start showing – much too late, as by this time the brain has already suffered significant damage. That’s why scientists want to find signs that appear earlier, even in those who are asymptomatic, which would offer opportunities to test drugs that could slow or even halt its progression.
One avenue worth exploring is urine. For years, the chemicals contained in this waste product have been used as an indicator of certain diseases, and some are even characterized by abnormal chemical composition, like some breast cancers. Indeed, studies on mice with models of Alzheimer’s have already found that one particular component is elevated in these rodents, and that increases are apparent prior to the onset of hallmark Alzheimer’s pathology – namely, an increase in toxic bundles of a protein called amyloid-β (Aβ).
To examine this idea further, researchers from the Monell Chemical Senses Center and the U.S. Department of Agriculture used three different rodent models of Alzheimer’s disease. Described in Scientific Reports, each had mutations in the gene responsible for the amyloid precursor protein (APP), the one that gets snipped up to generate Aβ. Similar to humans, these mutations lead to a buildup of Aβ, resulting in the characteristic brain plaques seen in Alzheimer’s patients.
The team wanted to see whether the urine of these animals contained changes in the levels of volatile chemicals, or those that are easily evaporated, so they devised a behavioral “sniff” test. Mice have a keen sense of smell and are highly motivated to seek out and investigate odors, so the team provided mice rodents with urine samples from the mutant rodents, alongside controls, and documented how long they spent sniffing each one. Significant differences in the time spent lingering over the mutant vs control samples indicated the presence of a potent smell in the former.
Mice can detect very small concentrations of odors. schankz/Shutterstock
Next, they performed chemical analyses on the samples to see if these apparent differences were detectable, which revealed the presence of unique odor “signatures” in the mutant mice. Interestingly, the changes didn’t include the appearance of any novel chemicals that were not present in the control mice, but rather alterations to the levels of existing compounds. This could indicate that the mutations are causing some kind of metabolic abnormality in the mice.
Perhaps most importantly, these urine signatures appeared prior to the development of detectable levels of plaque buildup in the brain, which indicates that the shift in chemical concentrations is a result of the mutated gene, rather than an effect of disease progression. This raises the possibility that similar biomarkers may exist in humans that could serve as early indicators of disease, although further studies will be needed to confirm this. But if that turns out to be the case, the researchers suggest it could be useful to combine this data with established tests, such as brain imaging and cognitive analysis.
