Inflammation in Alzheimer’s Disease: Cross-talk between Lipids and Innate Immune Cells of the Brain

Alzheimer's disease (AD) is distressingly common and age is the major risk factor. One of the challenges in AD research is the scarcity of information on the healthy aging brain, since many of features considered part of ‘AD pathology' – inflammation and oxidant stress – are also present in cognitively normal elderly populations. For this reason it is critical to study AD (and pre-AD) subjects in the context of age-matched controls, an essential feature of the data set which inspired this review. Our study of lipids in cerebrospinal fluid (CSF) of aged subjects is a novel data set, especially as lipids are relatively understudied in AD, with much of the experimental and clinical research literature focused on A-beta and tau. Inflammation too is often discussed as a consequence of rather than active participant in AD pathology. For these reasons we focus on the interplay between inflammation and lipids in the pathological process of AD, an interaction that is likely important in pathophysiology of AD. We present a summary of the complex CSF lipid changes found in our clinical AD studies, and focus in on a few of these changes to highlight the importance of lipid interactions with the brain immune system in the pathogenesis of AD, recognizing that our interpretation of these data requires further study. Neither the full complexity of the brain immune system nor the changes in lipids in CSF can be reviewed here, but we hope that the many interactions highlighted between lipids and the immune system will prompt others to investigate these pathophysiologic connections, leading to a greater understanding of the causes of AD.