title: Lipidomics of Alzheimer's disease: current status.
abstract: Alzheimer's disease (AD) is a cognitive disorder with a number of complex neuropathologies, including, but not limited to, neurofibrillary tangles, neuritic plaques, neuronal shrinkage, hypomyelination, neuroinflammation and cholinergic dysfunction. The role of underlying pathological processes in the evolution of the cholinergic deficit responsible for cognitive decline has not been elucidated.             Furthermore, generation of testable hypotheses for defining points of pharmacological intervention in AD are complicated by the large scale occurrence of older individuals dying with no cognitive impairment despite having a high burden of AD pathology (plaques and tangles). To further complicate these research challenges, there is no animal model that reproduces the combined hallmark neuropathologies of AD. These research limitations have stimulated the application of 'omics' technologies in AD research with the goals of defining biologic markers of disease and disease progression and uncovering potential points of pharmacological intervention for the design of AD therapeutics. In the case of sporadic AD, the dominant form of dementia, genomics has revealed that the ε4 allele of apolipoprotein E, a lipid transport/chaperone protein, is a susceptibility factor. This seminal observation points to the importance of lipid dynamics as an area of investigation in AD. In this regard, lipidomics studies have demonstrated that there are major deficits in brain structural glycerophospholipids and sphingolipids, as well as alterations in metabolites of these complex structural lipids, which act as signaling molecules. Peroxisomal dysfunction appears to be a key component of the changes in glycerophospholipid deficits. In this review, lipid alterations and their potential roles in the pathophysiology of AD are discussed.
authors.affiliation: Metabolomics Unit, Department of Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Parkway, Harrogate, TN 37752, USA. paul.wood@lmunet.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Wood