Accounting for up to 80% of all dementia cases, Alzheimer’s disease (AD) is a chronic neurodegenerative disease that affects multiple cognitive domains such as memory, language, visuospatial function, personality, and behavior. Pathological structures of AD include neurofibrillary tangles and the formation of amyloid-beta (Aβ) plaque deposits. AD can be characterized by the Aβ plaques which are formed from extracellular deposits of amyloid-beta peptide, a 40/42 amino acid long peptide cleaved from amyloid precursor protein (APP) by β and γ-secretase. The abnormal processing of APP leads to the formation of these Aβ plaques. Metabolites such as lipids are intermediates or products of cellular metabolism which reflect the state of the diseased AD brain. While lipid metabolism and amyloid pathology have been reported to have a high correlation, the exact mechanism behind the phenomena is unknown and requires further lipid profiling for elucidation.<br/><br/>To shed light on the amyloid pathology of AD, this project uses the analytical technique of mass spectrometry imaging (MSI) in conjunction with desorption electrospray ionization (DESI) to extract and study the lipid composition and spatial distribution in brain samples of the 5xFAD mouse models throughout early onset and progression of AD characterized by a few identifiable lipid markers. Several glycerophospholipids have expressed a decrease in abundance while fatty acids have increased throughout the pathogenesis of AD. Thereupon the observed lipid aberrations in the whole brain of early-onset AD pathogenesis indicate a perturbation of lipid metabolism. Future work involves monitoring the age-dependent formation of Aβ plaques using fluorescence imaging as an additional reference of AD progression.

Ambient ionization mass spectrometry imaging: Revealing amyloid pathology in Alzheimer’s disease

ACS Spring 2022

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