Abstract
Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of β-amyloid (Aβ). Disrupted Aβ kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profiles of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDI-TOF imaging MS (IMS) can determine the relative abundance and spatial distribution of specific lipids in different tissues. We used 5XFAD mice that almost exclusively generate and rapidly accumulate massive cerebral levels of Aβ-42 (1). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where Aβ plaques are first generated in AD. Our results suggest that MALDI-IMS is a powerful tool for analyzing the distribution of various phospholipids and that this application might provide novel insight into the prediction of disease.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia; at the present time there is no disease-modifying drug for AD
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
The applied binary matrix composed of dihydroxybenzoic acid (DHB) and ␣-cyano-4-hydroxycinnamic acid (CHCA) [17] was used to improve the detection of PLs in both modes of polarity
Summary
Alzheimer’s disease (AD) is the most common form of dementia; at the present time there is no disease-modifying drug for AD. P. Kim. Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer’s disease. 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. 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. 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
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