Research from the Monell Chemical Senses Center, Philadelphia, the US Department of Agriculture, and other collaborating institutions has found that urine samples from mouse models of Alzheimer’s disease show a uniquely identifiable odor signature before significant development of the disease’s brain pathology.
These findings, published in Scientific Reports, suggest that it may be possible to develop a non-invasive tool for early diagnosis of Alzheimer’s disease.
“Previous research from the USDA and Monell has focused on body odor changes due to exogenous sources such as viruses or vaccines. Now we have evidence that urinary odor signatures can be altered by changes in the brain characteristic of Alzheimer’s disease,” said Bruce Kimball, PhD, a chemical ecologist with the USDA National Wildlife Research Center (NWRC) who is stationed at the Monell Center, in a statement. “This finding may also have implications for other neurologic diseases.”
The researchers studied unique mouse lines that mimicked Alzheimer’s-related brain pathology. Because Alzheimer’s is only found in humans, the researchers created the Alzheimer’s mouse models, called APP mice, by introducing human genes associated with mutations of the amyloid-β precursor protein gene into the mouse genome. They then pharmacologically activated the genes to create excess amyloid-β protein, leading to plaque buildup in the brains of the mice.
Using both behavioral analyses and head-space gas chromatography/mass spectrometry (GC/MS), the researchers found that mice with the mutant APP gene expression had a uniquely identifiable odor in their urine that did not result from the appearance of new chemical compounds, but instead reflected a shift in concentrations of existing urinary compounds.
The odor differences were also mostly independent of age, and preceded detectible amounts of plaque build-up in the mice’s brains. This suggests that the odor is related to the presence of an underlying gene, rather than the development of pathological changes in the brain.
Using linear discrimination analysis, the researchers found that the GC/MS peak responses provided accurate (>84%) predictions of whether the urine came from APP mice or the control mice.
“While this research is at the proof-of-concept stage, the identification of distinctive odor signatures may someday point the way to human biomarkers to identify Alzheimer’s at early stages,” said Daniel Wesson, PhD, neuroscientist at the Case Western Reserve University School of Medicine in a statement.
The researchers noted that extensive studies are needed to identify and characterize odor signatures predictive of Alzheimer’s disease in humans.
Kimball BA, Wilson DA, Wesson DW. Alterations of the volatile metabolome in mouse models of Alzheimer’s disease. Sci Rep. 2016; doi:10.1038/srep19495.