Abstract: Described herein are methods for identifying mitochondrial defects using metabolomics and genetic analyses and using this information to stratify patients and to correct for metabolic defects in a precision medicine approach. One embodiment is a method for isolating and analyzing samples containing one or more mitochondrial biomarker metabolites or genetic markers useful for the analysis, identification, stratification or classification, and treatment of metabolic changes associated with a CNS or neuropsychiatric disease in a subject and therapies useful for the treatment thereof. In one aspect, the biomarker metabolites comprise mitochondrial metabolites including acylcarnitines and endocannabinoids and the genetic analyses focus on metabolic enzymes or transport mechanisms.

Abstract: Described herein are methods for identifying or diagnosing Alzheimer's disease or poor cognition in a subject or population of subjects by analyzing biomarkers. In one aspect, the biomarkers comprise liver function enzymes or metabolites including alanine aminotransferase (ALT), aspartate aminotransferase (AST), ratio of ALT to AST, alkaline phosphatase, albumin, bilirubin, cholesterol and cholesterol metabolites, amino acids, phospholipids, bile acids, or other metabolites. In another aspect, the biomarkers comprise alanine aminotransferase (ALT), aspartate aminotransferase (AST), or the ratio of ALT to AST levels. In another aspect, the marker comprises the genotype of the ALT or AST enzymes.

Abstract: Described herein are methods and composition for diagnosing and evaluating the treatment of depression using one or more biomarker metabolites for the diagnosis and monitoring treatment efficacy. In one aspect, the biomarker metabolites can be used to screen subjects for the likelihood of developing depression, the diagnosis thereof, monitoring the efficacy of treatment, and evaluating a subject's propensity for responding to treatment.

Abstract: Described herein are methods for stratifying Alzheimer's disease among male and female subjects by analyzing biomarker metabolites. In one aspect, the biomarker metabolite comprises one or more of PC ae C44:4, PC ac C44:5, or PA ae C44:6; or PC ac C44:4, PC ac C44:5, PC aa C32:1, PC aa C32:0, or PC ae C42:4.

Abstract: Embodiments of the present disclosure relate generally to the analysis and identification of global metabolic changes in Alzheimer's disease (AD). More particularly, the present disclosure provides materials and methods relating to the use of metabolomics as a biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance. Defining metabolic changes during AD disease trajectory and their relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.

Abstract: Embodiments of the present disclosure relate generally to the analysis of broad metabolic changes associated with neurological disorders. In particular, the present disclosure provides materials and methods relating to the use of metabolomics as a biochemical approach to identify peripheral metabolic changes and corresponding metabolic biomarkers of neurological disorders. Embodiments of the present disclosure include the use of bile acids and their derivatives as metabolic biomarkers to aid in the determination of whether a subject suffers from, or is at risk of developing, a neurological disorder, such as Alzheimer's Disease (AD).

Abstract: The present disclosure relates to compositions and methods for use in the analysis of broad metabolic changes associated with neurological disorders. In particular, the present disclosure provides materials and methods relating to the use of metabolomics as a biochemical approach to identify sex-specific metabolic biomarkers of neurological disorders. Embodiments of the present disclosure include the use of sex-specific metabolic biomarkers to aid in the determination of whether a subject suffers from, or is at risk of developing, a neurological disorder, such as Alzheimer's disease (AD).

Abstract: Disclosed herein are markers for diagnosing Alzheimer's Disease and/or mild cognitive impairment, for predicting risk of developing Alzheimer's Disease and/or mild cognitive impairment, and for monitoring the efficacy of treatment for Alzheimer's Disease and/or mild cognitive impairment. Also disclosed herein are methods of diagnosing Alzheimer's Disease and/or mild cognitive impairment in a subject in need thereof, for predicting risk of developing Alzheimer's Disease and/or mild cognitive impairment in a subject in need thereof, and for monitoring the efficacy of a treatment for Alzheimer's Disease and/or mild cognitive impairment in the subject.

Abstract: The present invention has utilized the power of lipidomics to profile lipid metabolites and to characterize changes in lipid metabolism as they relate to CNS disorders. Lipidomic signatures can guide the development of diagnostic, prognostic and surrogate markers for CNS disorders; identification of new targets for drug design based on highlighted perturbed pathways; stratify patients with CNS disorders as to which pathways are impaired, and facilitate the determination of which patients with CNS disorders are candidates for a particular therapy, i.e. provide the tools for a personalized approach to therapy; identify which patients are responding or are developing side effects to a treatment; design of modified antipsychotics that have less metabolic side effects and enhanced activity; overcome the lag phase in response to some treatments; and find better combination therapies for CNS disorders that target the pathways that are impaired (e.g., impairments in lipid and/or carbohydrate metabolism).

Abstract: The present invention concerns the application of lipidomics to statin treatment for disorders such as cardiovascular disorders. Hence, the invention provides, among other things, a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject following commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen. The invention further provides a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject before commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen.

Abstract: The present invention has utilized the power of lipidomics to profile lipid metabolites and to characterize changes in lipid metabolism as they relate to CNS disorders. Lipidomic signatures can guide the development of diagnostic, prognostic and surrogate markers for CNS disorders; identification of new targets for drug design based on highlighted perturbed pathways; stratify patients with CNS disorders as to which pathways are impaired, and facilitate the determination of which patients with CNS disorders are candidates for a particular therapy, i.e. provide the tools for a personalized approach to therapy; identify which patients are responding or are developing side effects to a treatment; design of modified antipsychotics that have less metabolic side effects and enhanced activity; overcome the lag phase in response to some treatments; and find better combination therapies for CNS disorders that target the pathways that are impaired (e.g., impairments in lipid and/or carbohydrate metabolism).

Abstract: The present invention concerns the application of lipidomics to statin treatment for disorders such as cardiovascular disorders. Hence, the invention provides, among other things, a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject following commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen. The invention further provides a method of correlating a lipid profile with a positive or negative response to a statin treatment regimen by obtaining a lipid profile of a sample from a mammalian subject before commencement of the treatment regimen; and correlating the lipid profile in the sample with a positive or negative response to the treatment regimen.