Methods for the diagnosis and risk assessment of plasmalogen deficiency mediated diseases of aging

Abstract

The present invention relates to methods for the diagnosis and risk assessment of plasmalogen deficiency mediated diseases of aging. The present invention describes the relationship between plasmalogen biosynthesis dysfunction and the biochemical and clinical manifestations of age related disorders. Specifically the present invention describes an increased prevalence of colon cancer, prostate cancer, lung cancer, breast cancer, ovary cancer, kidney cancer, cognitive impairment and dementia in subjects suffering from adult onset plasmalogen biosynthesis disorder (AO-PBD).

1 - 7 . (canceled) 
   
   
       8 . A method of diagnosing adult onset plasmalogen biosynthesis disorder, diagnosing a plasmalogen deficiency-related human health disorder, or the risk of a plasmalogen deficiency-related human health disorder in a subject, comprising the steps of:
 a) analyzing a sample from said subject to obtain quantifying data for one or more than one metabolite markers;   b) comparing said quantifying data for said one or more than one metabolite marker to corresponding data obtained from one or more than one reference sample to identify a decrease in the level of said one or more than one metabolite marker in said sample; and   c) using said decrease in level of said one or more than one metabolite marker in said sample for diagnosing the presence of adult onset plasmalogen biosynthesis disorder in said subject,   wherein the one or more than one metabolite marker comprises one or more than one molecule selected from the group consisting of: diacyl glycerylphosphoethanolamines, plasmanyl glycerylphosphoethanolamines, plasmenyl glycerylphosphoethanolamines, and free fatty acids.   
   
   
       9 . The method according to  claim 8 , further comprising:
 analyzing a sample from said subject to obtain quantifying data for one or more than one internal control metabolite; and   obtaining a ratio for each of the levels of said one or more than one metabolite marker to the level obtained for the one or more than one internal control metabolite;   wherein the comparing step (b) comprises comparing each ratio to one or more corresponding ratios obtained for the one or more than one reference sample.   
   
   
       10 . The method according to  claim 9 , wherein the diacyl glycerylphosphoethanolamines are selected from the group consisting of: PtdEt 16:0/18:0, PtdEt 16:0/18:1, PtdEt 18:0/18:0, PtdEt 18:0/18:1, and combinations thereof. 
   
   
       11 . The method according to  claim 9 , wherein the plasmanyl glycerylphosphoethanolamines are selected from the group consisting of: plasmanyl 16:0/18:1, plasmanyl 16:0/18:2, plasmanyl 16:0/20:4, plasmanyl 16:0/22:4, plasmanyl 16:0/22:6, plasmanyl 18:0/18:1, plasmanyl 18:0/18:2, plasmanyl 18:0/20:4, plasmanyl 18:0/22:4, plasmanyl 18:0/22:6, and combinations thereof. 
   
   
       12 . The method according to  claim 9 , wherein the plasmenyl glycerylphosphoethanolamines is selected from the group consisting of: plasmenyl 16:0/18:1, plasmenyl 16:0/18:2, plasmenyl 16:0/20:4, plasmenyl 16:0/22:4, plasmenyl 16:0/22:6, plasmenyl 18:0/18:1, plasmenyl 18:0/18:2, plasmenyl 18:0/20:4, plasmenyl 18:0/22:4, plasmenyl 18:0/22:6, and combinations thereof. 
   
   
       13 . The method according to  claim 9 , wherein the free fatty acid is selected from the group consisting of: free docosohexanoic acid (DHA) 22.6, free DHA 20:4 and combinations thereof. 
   
   
       14 . The method according to  claim 8 , wherein the plasmalogen deficiency-related disorder is selected from the group consisting of: breast cancer, colorectal cancer, prostate cancer, lung cancer, ovarian cancer, renal cancer, Alzheimer's Disease, Dementia, or Cognitive impairment. 
   
   
       15 . The method according to  claim 14 , wherein the subject is older than forty years of age. 
   
   
       16 . The method according to  claim 8 , wherein the quantifying data is obtained using a Fourier transform ion cyclotron resonance, time of flight, orbitrap, quadrupole or triple quadrupole mass spectrometer. 
   
   
       17 . The method according to  claim 16 , wherein the mass spectrometer is equipped with a chromatographic system. 
   
   
       18 . The method according to  claim 8 , wherein the sample is a blood sample. 
   
   
       19 . The method according to  claim 8 , wherein the sample is a blood serum sample. 
   
   
       20 . The method according to  claim 8 , wherein the sample is a cerebral spinal fluid sample. 
   
   
       21 . The method according to  claim 8 , wherein a liquid/liquid extraction is performed on the sample whereby non-polar metabolites are dissolved in an organic solvent and polar metabolites are dissolved in an aqueous solvent. 
   
   
       22 . The method according to  claim 21 , wherein the extracted samples are analyzed by electrospray ionization or atmospheric pressure chemical ionization. 
   
   
       23 . The method according to  claim 21 , wherein the extracted samples are analyzed by MS/MS transition. 
   
   
       24 . The method according to  claim 21 , wherein the extracted samples are analyzed by chromatography and MS/MS transition. 
   
   
       25 . The method according to  claim 24 , wherein the MS/MS transitions for the diacyl glycerylphosphatidylethanolamines are: 718.0/255.0, 716.0/255.0, 746.0/283.0 and 744.0/283.0, respectively. 
   
   
       26 . The method according to  claim 24 , wherein the MS/MS transitions for the plasmanyl glycerylphosphoethanolamines are: 702.0/281.0, 700.0/279.0, 724.0/303.0, 752.0/331.0, 748.0/327.0, 730.0/281.0, 728.0/279.0, 752.0/303.0, 780.0/331.0 and 776.0/327.0, respectively. 
   
   
       27 . The method according to  claim 24 , wherein the MS/MS transitions for the plasmenyl glycerylphosphoethanolamines are: 700.0/281.0, 698.0/279.0, 722.0/303.0, 750.0/331.0, 746.0/327.0, 728.0/281.0, 726.0/279.0, 750.6/303.2, 778.0/331.0 and 774.0/327.0, respectively. 
   
   
       28 . The method according to  claim 24 , wherein the MS/MS transitions for the free fatty acids are: 327.2/283.0 and 303.2/259.5, respectively.