Mass Spectrometry Imaging in Alzheimer's Disease

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 the upstream events that lead to Aβ plaque formation and its metabolism inside the brains. Matrix-assisted laser desorption ionization mass spectrometry imaging (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. MALDI-MSI visualized depositions of shorter peptides in AD brains; Aβ1-36 to Aβ1-39 were quite similarly distributed with Aβ1-40 as a vascular pattern, and deposition of Aβ1-42 and Aβ1-43 was visualized with a distinct senile plaque pattern distributed in parenchyma. Moreover, how MALDI-MSI covered lipidomics of plaque pathology has been reviewed, which is of interest as aberrations in neuronal lipid biochemistry have been implicated in AD pathogenesis. In this study, 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.