1H NMR-Based Metabolomic Signatures in Rodent Models of Sporadic Alzheimer's Disease and Metabolic Disorders.

Abstract

Alzheimer's disease (AD) is a chronic neurological disorder that impacts the elderly population all over the globe. Evidence suggests association between AD and metabolic disorders such as diabetes mellitus (DM) and obesity (OB). The present study is an attempt to evaluate metabolic alterations in the serum and brain through NMR spectroscopy with the aim to identify shared metabolic signatures. AD was induced in rats by stereotactic intracerebroventricular injection of oligomerized Aβ-42 peptide into the brain. DM and OB were induced by intraperitoneal injection of streptozotocin and feeding rats on a high-fat diet, respectively. The metabolic alterations obtained through ¹H NMR spectroscopy were further subjected to multivariate analysis by principal component analysis and partial least-squares discrimination for identification of metabolic signatures. In the serum, the levels of lactate and betaine were increased in AD, DM, and OB rats. On the other hand, the metabolite profile of brain indicated increase in the levels of lactate, N-acetylaspartate, and creatinine in AD, DM, and OB rats. Additionally, the concentration of neurochemicals such as glutamate, GABA, N-acetylglutamate, and myo-inositol were also elevated. The alterations in neurotransmitters and cerebral energy metabolism were accompanied by deficits in cognition assessed by Morris water maze in AD, DM, and OB rats. The perturbed metabolic profiles were accompanied by the presence of pathogenic amyloid deposits visualized by Congo red stain in the brains of AD, DM, and OB rats. Overall, the study identifies common metabolic signatures in AD, DM, and OB that may be involved in etiopathogenesis and also suggests linkages between these three conditions.