Mass Spectrometry Imaging in Alzheimer's Disease

INTRODUCTION Amyloid-beta (Aβ) pathology is the precipitating histopathological characteristic of Alzheimer's disease (AD). Although the formation of amyloid plaques in human brains is suggested to be a key factor in initiating AD pathogenesis, it is still not fully understood upstream events that lead to Aβ plaque formation and its metabolism inside the brains. METHODS Matrix assisted laser desorption ionization mass spectrometry (MALDI-MSI) has been successfully introduced to study AD pathology in brain tissue both in AD mouse models and human samples. By using MALDI-MSI, a highly selective deposition of Aβ peptides in AD brains with a variety of cerebral amyloid angiopathy (CAA) involvement was observed. RESULTS MALDI-MSI visualized depositions of shorter peptides in AD brains; A 1-36 to A1-39 were quite similarly distributed with A 1-40 as a vascular pattern, deposition of A 1-42 and A 1-43 were visualized with a distinct senile plaque pattern distributed in parenchyme. Moreover, how MALDI-MSI covered in situ lipidomics of plaque pathology has been reviewed, which is of interest as aberrations in neuronal lipid biochemistry have been implicated in AD pathogenesis. Discussion Here we introduce the methodological concepts and challenges of MALDI MSI for the studies of AD pathogenesis. Diverse Aβ isoforms including various C- and N-terminal truncations in AD and CAA brain tissues will be visualized. Despite the close relationship between vascular and plaque Aβ deposition, the current strategy will define cross-talk between neurodegenerative and cerebrovascular processes at the level of Aβ metabolism. Impact Statement Matrix assisted laser desorption ionization mass spectrometry based chemical imaging (MALDI MSI) has been successfully applied to comprehensively delineate spatial Aβ peptide- and neuronal lipid patterns in brains with AD. This rather new approach overcomes major limitations inherent to commonly used biochemical methods and opens up for both static and dynamic biochemical interrogation of amyloid aggregation in situ.

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