Cerebrospinal Fluid Profile of Lipid Mediators In Alzheimer’s Disease

Background: Alzheimer's disease (AD) develops into dementia over a period of several years, during which subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are used as intermediary diagnoses of increasing severity. Chronic neuroinflammation resulting from insufficient resolution is involved in the pathogenesis of AD and is associated with cognitive impairment. Specialized pro-resolving lipid mediators (LMs) that promote the resolution of inflammation may be valuable markers in AD diagnosis and as therapeutic targets.Methods: Liquid chromatography-tandem mass spectrometry was used to analyze pro-resolving and pro-inflammatory LMs in cerebrospinal fluid (CSF) from patients with cognitive impairment ranging from subjective impairment to a diagnosis of AD, and correlated to cognition, CSF tau and β-amyloid (Aβ), and an inflammation biomarker (YKL-40). Results: RvD4, neuroprotectin D1, MaR1, and RvE4 were lower in AD and/or MCI compared to SCI. The pro-inflammatory LTB4 and 15-HETE were higher in AD and MCI, respectively, while PGD2 and PGE2 were decreased in AD, compared to SCI. RvD4 was also negatively correlated to AD tangle biomarkers. Many differences were dependent on gender.Conclusion: In this exploratory study of the lipidome in CSF of AD, MCI and SCI, the results indicate a gender-dependent shift in the LM profile from pro-resolving to pro-inflammatory in progression to AD, suggesting that it may be of use as a biomarker when followed by confirmation by replication studies.