Lipid profile as a biomarker for early detection of neurological disorders
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.
1. A biomarker for detecting a neurological disorder, wherein the biomarker is a regression value derived from a lipid profile obtained by shotgun lipidomics, wherein the regression value is a single value, derived from stepwise multivariate regression analysis, that is sensitive to changes in abundance of lipid molecular species of the lipid profile, wherein a regression value of about 1 is indicative of a neurological disorder.
2. The biomarker of claim 1 , wherein the lipid profile comprises lipids from at least 15 different lipid classes.
3. The biomarker of claim 2 , wherein the lipid profile comprises lipids from at least 20 different lipid classes.
4. The biomarker of claim 3 , wherein the lipid classes are selected from the group consisting of choline glycerophospholipid, ethanolamine glycerophospholipid, phosphatidylinositol, phosphatidylglycerol, phosphatidylserine, lyso-choline glycerophospholipid, lyso-ethanolamine glycerophospholipid, phosphatidic acid, lyso-phosphatidic acid, sphingomyelin, galactosylceramide, glucosylceramide, sulfatide, free fatty acid, prostaglandins, triacylglycerol, diacylglycerol, monoacylglycerol, acyl-CoA, acylcarnitine, cholesterol and cholesterol esters, oxysterol, ceramide, cardiolipin, sphingoid base-1-phosphate, shingosine, lyso-sphingomyelin, gangliosides, and oxidized derivatives of each of the above.
5. The biomarker of claim 3 , wherein the lipid classes are selected from the group consisting of plasmalogen, sulfatide, ceramide, sphingoid base-1-phosphates, cholesterol, and cholesterol esters.
6. The biomarker of claim 1 , wherein the lipid profile further comprises lipids from at least 75 different lipid molecular species.
7. The biomarker of claim 6 , wherein the lipid profile further comprises lipids from at least 100 different lipid molecular species.
8. The biomarker of claim 7 , wherein the lipid molecular species are selected from the group consisting of over 1000 lipid molecular species.
9. The biomarker of claim 1 , wherein the neurological disorder is selected from the group consisting of Alzheimer's disease (AD), pre-AD, Parkinson's disease, multiple sclerosis, fronto-temporal dementia, bipolar disorder, or schizophrenia.
10. The biomarker of claim 1 , wherein the lipid profile is a plasma lipid profile or a lipid profile of cerebrospinal fluid.