Method for assessing and treating or preventing impaired plasma polar lipid levels

Abstract

The invention pertains to the use of a preparation for the manufacture of a composition for preventing or treating impaired plasma levels of one or more polar lipids such as phosphatidylcholines [PC] selected from the group consisting of phosphatidylcholine diacyl C36:6 [PC aa C36:6], phosphatidylcholine diacyl C38:0 [PC aa C38:0], phosphatidylcholine diacyl C38:6 [PC aa C38:6], phosphatidylcholine diacyl C40:6 [PC aa C40:6] and phosphatidylcholine acyl-alkyl C40:6 [PC ae C40:6] in a preclinical AD or MCI subject or a subject with a high likelihood of developing AD or MCI, and wherein said subject is administered with a composition comprising at least one, preferably at least two, most preferably all B vitamins selected from the group consisting of vitamin B6, vitamin B12 and vitamin B9.

1 . A method for treating a preclinical subject with Alzheimer's Disease (AD) or mild cognitive impairment (MCI), wherein the treatment results in inhibiting, suppressing, and/or decreasing impaired plasma phosphatidylcholine (PC) or phosphatidylethanolamine (PE) lipid levels, the method comprising administering to the subject a composition comprising at least one B vitamin selected from the group consisting of vitamin B6, vitamin B12 and vitamin B9. 
     
     
         2 . The method according to  claim 1 , wherein the composition comprises at least two B vitamins selected from the group consisting of vitamin B6, vitamin B12 and vitamin B9. 
     
     
         3 . The method according to  claim 2 , wherein the composition comprises vitamin B6, vitamin B12 and vitamin B9. 
     
     
         4 . The method according to  claim 1 , wherein the composition comprises per daily dosage or per 100 ml, at least one of:
 0.5-10000 μg vitamin B12;   0.5-100 mg vitamin B6; and   100-5000 μg folic acid.   
     
     
         5 . The method according to  claim 4 , wherein the composition comprises per daily dosage or per 100 ml:
 0.5-10000 μg vitamin B12;   0.5-100 mg vitamin B6; and   100-5000 μg folic acid.   
     
     
         6 . The method according to  claim 3 , wherein the composition comprises per daily dosage or per 100 ml, 0.5-100 mg vitamin B6, and 100-5000 μg folic acid. 
     
     
         7 . The method according to  claim 1 , wherein the plasma phosphatidylcholine (PC) or phosphatidylethanolamine (PE) lipids are of one or more polar lipids selected from the group consisting of C16:1 CE; C18:3 CE; C20:4 CE; PI(34:1); PI(38:2); PI(38:4); C16:0 CE; C18:2 CE; PA(34:3); PE(36:0); PE(38:0); aePC(36:0); aePC(38:0); aePC(38:4); aePC(40:4); 1PC(18:0); 1PC(18:3); 1PC(20:4); PC(36:1); PC(38:0); PC(38:4); PC(40:4); DSM(18:0); aePC(32:1); aePC(32:2); aePC(34:0); PC(44:2); SM(16:0); SM(18:0); SM(22:0); SM(24:0); SM(24:1); aePC(36:5); aePC(38:5); aePC(40:5); 1PC(20:5); 1PC(22:5); PC(36:5); PC(38:5); PC(40:5); PI(38:5); PI(40:5); C20:5 CE; C22:6 CE; aePC(38:6); aePC(40:6); aePE(40:6); PC(36:6); PC(38:6); PC(40:6); PC(42:6); PI(40:6); C22:5 CE; aePE(38:6); 1PE(22:6); PE(38:6); PE(40:6); PI(38:6); PC(40:7); PC(40:8); PC(42:10); PC(42:7); PC(42:8); PC(42:9); PE(40:7); 1PC(22:6); C19:0 CE; C19:1 CE; C20:0 CE; C20:1 CE; C20:3 CE; PE(34:1); PE(34:2); PE(36:1); PE(36:2); PE(36:3); PE(36:4); PE(38:3); PE(38:4); PE(40:4); PI(36:3); PI(38:3); PS(38:4); aePC(36:1); aePC(38:1); aePC(38:2); aePC(38:3); aePC(40:2); aePC(40:3); 1PC(20:3); PC(34:3); PC(36:3); PC(38:1); PC(38:2); PC(40:3); PE(40:5) 1PC 22:6; and/or PC 40:6. 
     
     
         8 . The method according to  claim 1 , wherein the composition further comprises one or more of uridine and cytidine, or salts, phosphates, acyl derivatives or esters thereof. 
     
     
         9 . The method according to  claim 1 , wherein the composition further comprises a lipid fraction comprising at least one of docosahexaenoic acid (22:6; DHA), eicosapentaenoic acid (20:5; EPA) and docosapentaenoic acid (22:5; DPA), or esters thereof. 
     
     
         10 . The method according  claim 1 , wherein the composition further comprises, per daily dose or per 100 ml composition, at least 500 mg of DHA, and at least 50 mg of uridine, calculated as the cumulative amount of uridine, deoxyuridine, uridine phosphates, nucleobase uracil and acylated uridine. 
     
     
         11 . The method according  claim 1 , wherein the composition comprises, per daily dose or per 100 ml composition:
 0.5-10000 μg vitamin B12;   0.5-100 mg vitamin B6;   100-5000 μg folic acid;   100-500 mg EPA,   1000-1500 mg DHA,   50-600 mg phospholipids,   200-600 mg choline,   400-800 mg UMP (uridine monophosphate),   20-60 mg vitamin E (alpha-TE),   60-100 mg vitamin C, and   40-80 μg selenium.   
     
     
         12 . The method according  claim 1 , wherein the subject is an elderly of at least 50 years of age, and not suffering from any cognitive deficits. 
     
     
         13 . A method for treating a preclinical AD or MCI subject, wherein the treatment results in inhibiting, suppressing, and/or decreasing impaired plasma levels of one or more phosphatidylcholines (PCs) selected from the group consisting of phosphatidylcholine diacyl C36:6 [PC aa C36:6], phosphatidylcholine diacyl C38:0 [PC aa C38:0], phosphatidylcholine diacyl C38:6 [PC aa C38:6], phosphatidylcholine diacyl C40:6 [PC aa C40:6] and phosphatidylcholine acyl-alkyl C40:6 [PC ae C40:6], the method comprising administering to the subject a comprising at least one B vitamin selected from the group consisting of vitamin B6, vitamin B12 and vitamin B9. 
     
     
         14 . The method according to  claim 13 , wherein the composition comprises at least two B vitamins selected from the group consisting of vitamin B6, vitamin B12 and vitamin B9. 
     
     
         15 . The method according to  claim 14 , wherein the composition comprises vitamin B6, vitamin B12 and vitamin B9. 
     
     
         16 . The method according to  claim 13 , wherein the one or more phosphatidylcholines are at least two phosphatidylcholine species selected from the group consisting of phosphatidylcholine diacyl C36:6 [PC aa C36:6], phosphatidylcholine diacyl C38:0 [PC aa C38:0], phosphatidylcholine diacyl C38:6 [PC aa C38:6], phosphatidylcholine diacyl C40:6 [PC aa C40:6] and phosphatidylcholine acyl-alkyl C40:6 [PC ae C40:6]. 
     
     
         17 . The method according to  claim 13 , wherein the one or more phosphatidylcholine species is selected from the group consisting of phosphatidylcholine diacyl C36:6 [PC aa C36:6], phosphatidylcholine diacyl C38:6 [PC aa C38:6], phosphatidylcholine diacyl C40:6 [PC aa C40:6] and phosphatidylcholine acyl-alkyl C40:6 [PC ae C40:6]. 
     
     
         18 . The method according to  claim 17 , wherein the polar lipids are phosphatidylcholine diacyl C40:6 [PC aa C40:6] and/or phosphatidylcholine acyl-alkyl C40:6 [PC ae C40:6]. 
     
     
         19 . The method according to  claim 13 , wherein the plasma PC levels are monitored in the subject before and/or after administration. 
     
     
         20 . A method for treating a preclinical AD or MCI subject, wherein the treatment results in inhibiting, suppressing, and/or decreasing impaired plasma polar lipid levels in a subject with a high likelihood of developing AD or MCI, comprising:
 (a) analyzing plasma levels of at least one plasma polar lipid in a subject, wherein the plasma polar lipid is a phosphatidylcholine (PC) or phosphatidylethanolamine (PE) lipid;   (b) selecting a subject having an impaired plasma level of one or more of the plasma polar lipids;   (c) administering to the selected subject a composition comprising at least one B vitamin selected from the group consisting of vitamin B6, vitamin B12 and vitamin B9.   
     
     
         21 . The method according to  claim 20 , wherein the composition comprises vitamin B6, vitamin B12 and vitamin B9. 
     
     
         22 . The method according to  claim 20 , wherein the composition further comprises one or more of uridine and cytidine, or salts, phosphates, acyl derivatives or esters thereof. 
     
     
         23 . The method according to  claim 20 , wherein the plasma polar lipid is selected from the group consisting of C16:1 CE; C18:3 CE; C20:4 CE; PI(34:1); PI(38:2); PI(38:4); C16:0 CE; C18:2 CE; PA(34:3); PE(36:0); PE(38:0); aePC(36:0); aePC(38:0); aePC(38:4); aePC(40:4); 1PC(18:0); 1PC(18:3); 1PC(20:4); PC(36:1); PC(38:0); PC(38:4); PC(40:4); DSM(18:0); aePC(32:1); aePC(32:2); aePC(34:0); PC(44:2); SM(16:0); SM(18:0); SM(22:0); SM(24:0); SM(24:1); aePC(36:5); aePC(38:5); aePC(40:5); 1PC(20:5); 1PC(22:5); PC(36:5); PC(38:5); PC(40:5); PI(38:5); PI(40:5); C20:5 CE; C22:6 CE; aePC(38:6); aePC(40:6); aePE(40:6); PC(36:6); PC(38:6); PC(40:6); PC(42:6); PI(40:6); C22:5 CE; aePE(38:6); 1PE(22:6); PE(38:6); PE(40:6); PI(38:6); PC(40:7); PC(40:8); PC(42:10); PC(42:7); PC(42:8); PC(42:9); PE(40:7); 1PC(22:6); C19:0 CE; C19:1 CE; C20:0 CE; C20:1 CE; C20:3 CE; PE(34:1); PE(34:2); PE(36:1); PE(36:2); PE(36:3); PE(36:4); PE(38:3); PE(38:4); PE(40:4); PI(36:3); PI(38:3); PS(38:4); aePC(36:1); aePC(38:1); aePC(38:2); aePC(38:3); aePC(40:2); aePC(40:3); 1PC(20:3); PC(34:3); PC(36:3); PC(38:1); PC(38:2); PC(40:3); and PE(40:5).