Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

Journal Article · Fri Dec 07 00:00:00 EST 2012 · Journal of Proteome Research, 11(12):5903-5913

DOI:https://doi.org/10.1021/pr300666p· OSTI ID:1060125

Hu, Zeping; Browne, Edward R; Liu, Tao; Angel, Thomas E; Ho, Paul C; Chun Yong Chan, Eric

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, non-targeted metabotyping 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 (Q28 Y = 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 (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 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

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1060125
• Report Number(s): PNNL-SA-90706; 400412000
• Journal Information: Journal of Proteome Research, 11(12):5903-5913, Journal Name: Journal of Proteome Research, 11(12):5903-5913
• Country of Publication: United States
• Language: English