Mass Spectrometry Imaging in Alzheimer's Disease

• Introduction: Amyloid-beta (A beta) 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 A beta plaque formation and its metabolism inside the brains.Methods: 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 A beta 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 beta 1-36 to A beta 1-39 were quite similarly distributed with A beta 1-40 as a vascular pattern, and deposition of A beta 1-42 and A beta 1-43 was visualized with a distinct senile plaque pattern distributed in parenchyma. 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: In this study, we introduce the methodological concepts and challenges of MALDI-MSI for the studies of AD pathogenesis. Diverse A beta 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 A beta deposition, the current strategy will define cross talk between neurodegenerative and cerebrovascular processes at the level of A beta metabolism. Impact statementMatrix-assisted laser desorption ionization mass spectrometry-based chemical imaging has been successfully applied to comprehensively delineate spatial A beta peptide- and neuronal lipid patterns in brains with Alzheimer's disease. This rather new approach overcomes major limitations inherent to commonly used biochemical methods and opens up for both static and dynamic biochemical interrogations of amyloid aggregation in situ.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

amyloid-beta

cerebral amyloid angiopathy

gangliosides

lipids

mass spectrometry imaging

proteoform

sphingolipids

sulfatides

amyloid-beta-protein

laser-desorption ionization

human spinal-cord

a-beta

precursor protein

mouse-brain

electrospray-ionization

transmembrane domain

peptides

tissue

Neurosciences & Neurology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)