title: Alterations of the volatile metabolome in mouse models of Alzheimer's disease.
abstract: In the present study, we tested whether the volatile metabolome was altered by mutations of the Alzheimer's disease (AD)-implicated amyloid precursor protein gene (APP) and comprehensively examined urinary volatiles that may potentially serve as candidate biomarkers of AD. Establishing additional biomarkers in screening populations for AD will provide enhanced diagnostic specificity and will be critical in evaluating disease-modifying therapies. Having strong evidence of gross changes in the volatile metabolome of one line of APP mice, we utilized three unique mouse lines which over-express human mutations of the APP gene and their respective non-transgenic litter-mates (NTg). Head-space gas chromatography/mass spectrometry (GC/MS) of urinary volatiles uncovered several aberrant chromatographic peak responses. We later employed linear discrimination analysis and found that the GC/MS peak responses provide accurate (>84%) genotype classification of urinary samples. These initial data in animal models show that mutant APP gene expression entails a uniquely identifiable urinary odor, which if uncovered in clinical AD populations, may serve as an additional biomarker for the disease.
authors.affiliation: United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National Wildlife Research Center, Monell Chemical Senses Center, Philadelphia, PA 19104.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Kimball
authors.affiliation: Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, 10962.|Department of Child &Adolescent Psychiatry, New York University School of Medicine, New York, NY, 10016.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Wilson
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106.|Department of Biology, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Wesson
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D005838:Genotype; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009812:Odorants
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers