Lipids, brain ageing, dementia, and lipidomics

Abstract Lipids represent a ubiquitous and structurally diverse biopolymer group, prevalent throughout the body. They are particularly abundant in the brain where they represent more than 50% of the brain's dry weight, and subserve essential structural and functional roles. As structural constituents of the plasma membranes of neurons and other brain cells, they contribute to neuronal membrane properties, including flexibility, permeability, lipid raft formation, and protein-lipid interactions, and physiological functions such as neuroplasticity and synaptic signaling. Many lipids are synthesized endogenously in peripheral organs such as liver and adipose tissue, and also in the central nervous system (CNS), while a few are essential dietary lipids. All have complex mechanisms of transport in plasma, where they are conveyed on carrier particles such as high- and low-density lipoprotein. In addition to their important structural roles, lipids and their metabolic derivatives such as isoprostanes, leukotrienes, prostaglandins, and endocannabinoids serve important signaling and molecular messenger roles, but can also reflect levels of oxidative stress or dysregulation in disease. In this review, we explore the diversity of lipid roles with a focus on brain function in the ageing CNS and dementia.