Washington University

Other

Platomics, Inc.

Xianlin Han

Richard W Gross

David Michael Holtzman

Gang Sun

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.

Lipid profile as a biomarker for early detection of neurological disorders

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/HO 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.

Multiplexing matrix-analyte stereo electronic interactions for high throughput shotgun metabolomics

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.

Multidimensional mass spectrometry of serum and cellular lipids directly from biologic extracts

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.

Molecular fingerprinting of triglycerides in biological samples by electrospray ionization tandem mass spectrometry

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.

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Clayton, MO, United States of America

Xianlin Han