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: 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: The present invention relates to compositions and methods for the early detection or monitoring of neurodegenerative diseases and neurological disorders including Alzheimer's disease. The invention provides biomarkers based on lipid profiles of biological samples and methods for using the biomarkers for the detection of neurodegenerative diseases and neurological disorders.

Abstract: A shotgun metabolomics approach using MALDI-tandem mass spectrometry was developed for the rapid analysis of cellular metabolites. Through the use of neutral organic solvents to inactivate endogenous enzyme activities (i.e., methanol/chloroform/H2O extraction), multiplexed extraction conditions and combinatorial alterations in matrix stereoelectronic composition and analyte interactions, multiple suites of metabolites were directly ionized and quantitated directly from biologic extracts without the need for prior chromatographic separation. Through combinatorial alterations in 9-aminoacridine charge, aromaticity and stacking, a set of multiplexed conditions was developed that allowed identification of many hundreds of peaks corresponding to metabolites from mouse heart extracts. Identification of metabolite peaks was based on mass accuracy and isomeric species were assigned based on diagnostic fragment ions present during tandem mass spectrometry for many of the identified metabolite peaks.

Abstract: A method for determination of at least one of the lipid species in a biological sample comprising subjecting the sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to multidimensional electrospray ionization mass spectrometry using either precursor ion or neutral loss scanning (or both) of all naturally occurring aliphatic chains, lipid fragments and precursor ions leading to observed fragments to generate a multidimensional matrix whose contour densities provides structural and quantitative information directly without chromatography. A method for determination of lipid content and/or lipid molecular species composition and quantity directly from lipid extracts of a biological sample comprising subjecting said lipid extract to electrospray ionization multidimensional mass spectrometry by comparisons to standards and algorithms described herein.

Abstract: A method for determination of at least one of the lipid species in a biological sample comprising subjecting the sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to multidimensional electrospray ionization mass spectrometry using either precursor ion or neutral loss scanning (or both) of all naturally occurring aliphatic chains, lipid fragments and precursor ions leading to observed fragments to generate a multidimensional matrix whose contour densities provides structural and quantitative information directly without chromatography. A method for determination of lipid content and/or lipid molecular species composition and quantity directly from lipid extracts of a biological sample comprising subjecting said lipid extract to electrospray ionization multidimensional mass spectrometry by comparisons to standards and algorithms described herein.

Abstract: A shotgun metabolomics approach using MALDI-tandem mass spectrometry was developed for the rapid analysis of cellular metabolites. Through the use of neutral organic solvents to inactivate endogenous enzyme activities (i.e., methanol/chloroform/H2O extraction), multiplexed extraction conditions and combinatorial alterations in matrix stereoelectronic composition and analyte interactions, multiple suites of metabolites were directly ionized and quantitated directly from biologic extracts without the need for prior chromatographic separation. Through combinatorial alterations in 9-aminoacridine charge, aromaticity and stacking, a set of multiplexed conditions was developed that allowed identification of many hundreds of peaks corresponding to metabolites from mouse heart extracts. Identification of metabolite peaks was based on mass accuracy and isomeric species were assigned based on diagnostic fragment ions present during tandem mass spectrometry for many of the identified metabolite peaks.

Abstract: The present invention relates to compositions and methods for the early detection or monitoring of neurodegenerative diseases and neurological disorders including Alzheimer's disease. The invention provides biomarkers based on lipid profiles of biological samples and methods for using the biomarkers for the detection of neurodegenerative diseases and neurological disorders.

Abstract: A method for determination of at least one of the triglyceride molecular species in a biological sample comprising the subjecting sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to 2D electrospray ionization tandem mass spectrometry (ESI/MS/MS) with neutral loss scanning of all naturally occurring aliphatic chains and contour analysis of 2D intercept peaks. A method for determination of tricylglyceride content and/or TG molecular species directly from a lipid extract of a biological sample comprising subjecting said lipid extract to electrospray ionization tandem mass spectrometry.

Abstract: A method of treating a living mammal having diabetic cardiomyopathy comprises administering an effective amount of an inhibitor to the mammal performing a shotgun lipidomics analysis on the mammal and determining that the treatment was successful when and if serum or tissue biopsy cardiolipin levels are increased and/or lysocardiolipin levels are decreased.

Abstract: A method for determination of at least one of the lipid species in a biological sample comprising subjecting the sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to multidimensional electrospray ionization mass spectrometry using either precursor ion or neutral loss scanning (or both) of all naturally occurring aliphatic chains, lipid fragments and precursor ions leading to observed fragments to generate a multidimensional matrix whose contour densities provides structural and quantitative information directly without chromatography. A method for determination of lipid content and/or lipid molecular species composition and quantity directly from lipid extracts of a biological sample comprising subjecting said lipid extract to electrospray ionization multidimensional mass spectrometry by comparisons to standards and algorithms described herein.

Abstract: A method for diagnosing Alzheimer's disease even at early stages by assessing the levels of sulfatides or its metabolites in biological fluids is disclosed.

Abstract: A method for determination of at least one of the lipid species in a biological sample comprising subjecting the sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to multidimensional electrospray ionization mass spectrometry using either precursor ion or neutral loss scanning (or both) of all naturally occurring aliphatic chains, lipid fragments and precursor ions leading to observed fragments to generate a multidimensional matrix whose contour densities provides structural and quantitative information directly without chromatography. A method for determination of lipid content and/or lipid molecular species composition and quantity directly from lipid extracts of a biological sample comprising subjecting said lipid extract to electrospray ionization multidimensional mass spectrometry by comparisons to standards and algorithms described herein.

Abstract: A method for determination of at least one of the triglyceride molecular species in a biological sample comprising the subjecting sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to 2D electrospray ionization tandem mass spectrometry (ESI/MS/MS) with neutral loss scanning of all naturally occurring aliphatic chains and contour analysis of 2D intercept peaks. A method for determination of tricylglyceride content and/or TG molecular species directly from a lipid extract of a biological sample comprising subjecting said lipid extract to electrospray ionization tandem mass spectrometry.

Abstract: A method for diagnosing Alzheimer's disease even at early stages by assessing the levels of sulfatides or its metabolites in biological fluids is disclosed.