A metabolomic study of the CRND8 transgenic mouse model of Alzheimer's disease

Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions

“…Metabotyping of the brain of two mouse models of AD, CRND8 and Tg2576 mice, identified common markers, with noticeable decreases in glutamate, N-acetylaspartate, creatine, gamma-aminobutyric acid and phosphocholine (Lalande et al 2014;Salek et al 2010). Our MSEA reveals that the metabolism of glutamate is significantly affected (Tab.…”

Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer’s disease

“…Decreased NAA, glutamate, glutamine, taurine, γ-amino butyric acid, choline and phosphocholine, creatine, phosphocreatine and succinate; and increased lactate, aspartate, glycine and other amino-acids including alanine, leucine, iso-leucine, valine and watersoluble free fatty-acids (0.8-0.9 and 1.2-1.3 ppm) in six affected regions [35] Alterations in tyrosine, tryptophan, purine, and tocopherol pathways; reductions in norepinephrine and its metabolites [38] Nine potential diagnostic biomarkers (LPCs, trypto phan, dihydrosphingosine, phytosphingosine and hexadecasphinganine) identified for AD [41] Eight sphingomyelin species significantly lower in AD; two ceramide species (N16:0 and N21:0) increased in AD; ratios of ceramide to sphingomyelin species differed significantly between groups; both N20:2 SM and OH-N25:0 ceramides were correlated with MMSE in AD [43] Omega-3 fatty acids indicative of MCI; elevated glyco proteins may be a risk for AD [46] CSF, cerebrospinal fluid; LC-ECA, liquid chromatography-electrochemical array; LPC, lysophosphatidyl choline; MDMS-SL, multi-dimensional mass spectrometry-based shotgun lipidomics; MMSE, mini-mental state examination; MS, mass spectrometry; NAA, N-acetyl-L-aspartate; NMR, nuclear magnetic resonance spectroscopy; SM, sphingomyelin; UPLC, ultra-performance liquid chromatography.…”

“…The affected regions were the hippocampus, cerebral cortex, frontal cortex, midbrain and cerebellum, with hippocampal and cortical regions being the most extensively involved, demonstrating widespread metabolic disturbances in AD, even involving the cerebellum and midbrain [35] .…”

“…Therefore, NAA may reflect the energy status of neurons as a marker of their dysfunction, but is not a marker of healthy neurons or total neuronal density [35] . These results suggest that metabolomic disturbances occur at an early stage of AD, even before detectable neuropathology.…”

Metabolomics in the Study of Alzheimer's Disease

“…The broad information obtained by metabolic fingerprinting approach make it the most attractive and suitable strategy for biomarker discovery [85], while at the same time, represents the most challenging and time-consuming approach in Metabolomics. In AD research, the obtaining of metabolic fingerprints is a recent practice by using both NMR [87][88][89] and MS-based [90][91][92][93][94] techniques.…”