Imaging mass spectrometry (IMS) of cortical lipids from preclinical to severe stages of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples. The present study uses the matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), permitting the direct anatomical analysis of lipids in postmortem brain sections from AD patients, which are compared with the intensity of the lipid signal in samples from matched subjects with no neurological diseases. The frontal cortex samples from AD patients were classified in three groups based on Braak's histochemical criteria, ranging from non-cognitively impaired patients to those severely affected. The main results indicate a depletion of different sulfatide lipid species from the earliest stages of the disease in both white and gray matter areas of the frontal cortex. Therefore, the decrease in sulfatides in cortical areas could be considered as a marker of the disease, but may also indicate neurochemical modifications related to the pathogenesis of the disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Interaction of Aβ42 with Membranes Triggers the Self-Assembly into Oligomers

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Regional differences in brain glucose metabolism determined by imaging mass spectrometry

“…The brain exhibits huge variability and specificity in lipid composition [20] . IMS has revealed novel long-term alterations in regional brain lipid distribution in neurodegenerative diseases [21] , [22] . However, since the brain does not use lipids as a major fuel source, changes in lipid composition reflect long-term changes, in contrast to the acute alterations seen with glucose metabolism [23] , [24] .…”

Higher Mass Accuracy MALDI‐TOF/TOF Lipid Imaging of Human Brain Tissue in Alzheimer's Disease

“…MALDI-IMS has been applied to various tissues and diseases such as cancer (Hiraide et al, 2016) and heart disease (Angel et al, 2016) and, more recently, in the brain to understand the lipid changes in alcohol-related brain damage (de la Monte et al, 2018), AD (Gónzalez de San Román, Manuel, Giralt, Ferrer, & Rodríguez-Puertas, 2017;Mendis, Grey, Faull, & Curtis, 2016), or the lipid cytoarchitecture of regions such as the subventricular zone (Hunter, Demarais, Faull, Grey, & Curtis, 2018). We have previously described a robust methodology for maximizing peptide ionization from formalin-fixed frozen human brain tissue (O'Rourke et al, 2018).…”