Molecular imaging of amyloid beta peptide in the Alzheimer brain
EMSL Project ID
47694
Abstract
The amyloid plaque is a principal pathological hallmark of the Alzheimer disease (AD) brain. Amyloid plaques are extracellular accumulations composed of the amyloid beta (Abeta) peptide and associated proteins. Little is known about the full plaque ‘proteome’ or the spatial localization of its components. Immunohistochemistry (IHC) has identified several proteins that colocalize with Abeta in the amyloid plaque; however this technique does not robustly lead to the discovery of novel associated proteins. Laser capture microscopy (LCM) followed by LC-MS/MS has been employed to further investigate the plaque proteome. For this method tryptic digestion of the plaque material is necessary and consequently data about plaque morphology is lost. Here we propose to investigate the amyloid plaque in detail by combining confocal microscopy and imaging mass spectrometry. Cryosections of human AD post mortem material will be used and plaques will initially be selected using a fluorescent IHC and confocal microscopy approach. Selected regions of interest will subsequently be investigated using the EMSL imaging mass spectrometry facilities. Data obtained by imaging mass spectrometry will be compared with data obtained using the LCM LC-MS/MS approach operational in our laboratory. This study will yield insight on the components that make up the AD amyloid plaque and their spatial orientation.
Project Details
Project type
Limited Scope
Start Date
2012-10-15
End Date
2012-12-15
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members