<sup>1</sup>H NMR-Based Metabolomic Signatures in\nRodent Models of Sporadic Alzheimer’s Disease and Metabolic\nDisorders

Alzheimer’s disease (AD) is a chronic neurological\ndisorder\nthat impacts the elderly population all over the globe. Evidence suggests\nassociation between AD and metabolic disorders such as diabetes mellitus\n(DM) and obesity (OB). The present study is an attempt to evaluate\nmetabolic alterations in the serum and brain through NMR spectroscopy\nwith the aim to identify shared metabolic signatures. AD was induced\nin rats by stereotactic intracerebroventricular injection of oligomerized\nAβ-42 peptide into the brain. DM and OB were induced by intraperitoneal\ninjection of streptozotocin and feeding rats on a high-fat diet, respectively.\nThe metabolic alterations obtained through <sup>1</sup>H NMR spectroscopy\nwere further subjected to multivariate analysis by principal component\nanalysis and partial least-squares discrimination for identification\nof metabolic signatures. In the serum, the levels of lactate and\nbetaine were increased in AD, DM, and OB rats. On the other hand,\nthe metabolite profile of brain indicated increase in the levels of\nlactate, <i>N</i>-acetylaspartate, and creatinine in AD,\nDM, and OB rats. Additionally, the concentration of neurochemicals\nsuch as glutamate, GABA, <i>N</i>-acetylglutamate, and myo-inositol\nwere also elevated. The alterations in neurotransmitters and cerebral\nenergy metabolism were accompanied by deficits in cognition assessed\nby Morris water maze in AD, DM, and OB rats. The perturbed metabolic\nprofiles were accompanied by the presence of pathogenic amyloid deposits\nvisualized by Congo red stain in the brains of AD, DM, and OB rats.\nOverall, the study identifies common metabolic signatures in AD, DM,\nand OB that may be involved in etiopathogenesis and also suggests\nlinkages between these three conditions.