Cerebrospinal fluid lipid signature as an indicator of risk and rate of progression from mild cognitive impairment to Alzheimer’s Disease

Abstract Background Lipids and lipid intermediates are essential for brain functions. Lipid dysregulation and its role in Alzheimer’s Disease (AD) pathogenesis is well documented. However, little is known about the role of lipids in progression and the rate of progression from Mild Cognitive Impairment (MCI) to AD. Our objective was to determine Cerebrospinal Fluid (CSF) lipids that could be implicated in the progression or rate of progression from MCI to AD. Method We analyzed the CSF lipid profile of patients with MCI (N = 92) by liquid chromatography coupled with mass spectrometry. The association of lipids with progression was studied by logistic regression and a Cox regression model was used to assess lipids associated with the speed of progression from MCI to AD. We adjusted our analyses for age, sex, core CSF AD biomarkers, APOE4 status, and MMSE. Result Forty‐eight (53%) MCI patients progressed to AD during follow‐up (58 ± 12.5 months). Two lipids were associated with progression, of which one as a risk factor (OR 9.288, 95% CI [1.67 – 51.65], p = 0.011) and one as protector (OR 0.048, 95% CI [0.048 – 0.989], p = 0.048). Five lipids were associated with the rate of progression, of which three were associated with a shorter time to progression (OR 2.449, 99% CI [1.226 – 4.892], p = 0.011; OR 2.227, CI 99% [1.119 – 4.430], p = 0.023; and OR 2.542, 99% CI [1.184 – 5.455], p = 0.017) and two with a longer time to progression (OR 0.173, 99% CI [0.066 – 0.449], p < 0.001; and OR 0.442, CI 99% [0.231 – 0.845], p = 0.014). Conclusion Our results suggest that lipid dysregulation could have an important role in progression and rate of progression from MCI to AD. Our data also indicate that CSF lipid alterations could have clinical implications as biomarkers of progression and speed of progression.