This article is available online at http://www.jlr.org Several hypotheses regarding the cause of AD have been proposed, among which the amyloid hypothesis is the most widely accepted ( 2 ). According to this hypothesis, AD is caused by abnormal accumulation of misfolded  -amyloid (A  ), a sequential cleavage product produced from amyloid precursor protein (APP) by  -and ␥ -secretases, and hyperphosphorylated tau protein. Several lines of evidence support the idea that A  can trigger the hyperphosphorylation of tau, resulting in neuronal degeneration in the brain ( 3, 4 ).There is evidence that FFAs are associated with several signaling processes related to the pathogenesis of AD. In particular, palmitic and stearic acid induce AD by triggering hyperphosphorylation of tau protein ( 5 ). Membrane phospholipids (PLs) are a prominent source of FFAs. Under disease conditions, phospholipase enzymes are produced in excess, inducing the hydrolysis of PLs and the release of FFAs. It is reasonable to hypothesize that alterations in PL concentrations are closely related to the pathogenesis of AD, as PLs perform a number of important cellular roles, including stabilization of membrane ion channels, neurotransmission, and the localization of A  plaques to PL cores ( 6, 7 ).As a result of progress in MS, and MALDI-imaging MS (IMS) in particular, the analysis of PL changes during disease progression has become feasible. MALDI-IMS is a unique tool that integrates molecular and histological information together with information attained using Alzheimer's disease (AD), the most common form of dementia, is primarily caused by abnormal protein kinesis and the accumulation of aggregated proteins in the brain.
This work was supported