Conclusion
These results in older adults show that blood lipids affect lipid profiles in CSF and such profiles are modified by APOE status. This suggests that how the CNS handles lipids may be important in the AD phenotype.
Methods
Older adults (n = 21, age 67.7 ± 8.6) underwent a 5-h TG and saline infusion on different days in random crossover design; lumbar CSF was collected at the end of the infusion. Lipids were extracted using dichloromethane/methanol and 13 classes of lipids analyzed using the Lipidyzer platform consisting of an AB Sciex 5500 MS/MS QTraps system equipped with a SelexION for differential mobility spectrometry (DMS). Multiple reaction monitoring was used to target and quantify 1070 lipids in positive and negative ionization modes with and without DMS.
Results
The TG infusion increased total lipids in the CSF, including the appearance of more lipids at the detection limit in the TG samples compared to saline (Chi square p < 0.0001). The infusion increased the total level of diacylglycerols and lysophosphatidylcholines and reduced dihydroceramides. Of the possible 1070 lipids detectable, we found 348 after saline and 365 after TG infusion. Analysis using MetaboAnalyst revealed 11 specific lipids that changed; five of these lipids decreased after TG infusion, and four of them differed by E4 status, but none differed by cognitive diagnosis or sex.