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Irregularities in lipid metabolism have been linked to numerous neurodegenerative diseases. The roles of abnormal brain, plasma, and cerebrospinal fluid (CSF) lipid levels in Alzheimer's disease (AD) onset and progression specifically have been described to a great extent in the literature. Apparent hallmarks of AD include, but are not limited to, genetic predisposition involving the APOE Ɛ4 allele, oxidative stress, and inflammation. A common culprit tied to many of these hallmarks is disruption in brain lipid homeostasis. Therefore, it is important to understand the roles of lipids, under normal and abnormal conditions, in each process. Lipid influences in processes such as inflammation and blood-brain barrier (BBB) disturbance have been primarily studied via biochemical-based methods. There is a need, however, for studies focused on uncovering the relationship between lipid irregularities and AD by molecular-based quantitative analysis in transgenic animal models and human samples alike. In this review, mass spectrometry as it has been used as an analytical tool to address the convoluted relationships mentioned above is discussed. Additionally, molecular-based mass spectrometry strategies that should be used going forward to further relate structure and function relationships of lipid irregularities and hallmark AD pathology are outlined.

Mass Spectrometry-Based Analysis of Lipid Involvement in Alzheimer’s Disease Pathology—A Review