Metabonomic profiling of TASTPM transgenic Alzheimer's disease mouse model.
Identification of molecular mechanisms underlying early stage Alzheimer's disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, nontargeted metabonomics of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild-type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild-type mice (Q2Y=0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D-fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D-galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type mice. Our results provided insights on the pathogenesis of APP-induced AD and reinforced the role of TASTPM in drug and biomarker development.
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543.
Ze-Ping
ZP
Hu
Edward R
ER
Browne
Tao
T
Liu
Thomas E
TE
Angel
Paul C
PC
Ho
Eric Chun Yong
EC
Chan
D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D050260:Carbohydrate Metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005942:Gluconates / Q000097:blood; D005947:Glucose / Q000737:chemistry; D006854:Hydrocortisone / Q000097:blood; D007124:Immunoenzyme Techniques; D019787:Linoleic Acid / Q000097:blood; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011374:Progesterone / Q000378:metabolism
D000596:Amino Acids; D015415:Biomarkers; D005942:Gluconates; D011374:Progesterone; D019787:Linoleic Acid; D005947:Glucose; C030691:gluconic acid; D006854:Hydrocortisone