Bio-imaging of metals in a mouse model of Alzheimer's disease by laser ablation inductively coupled plasma mass spectrometry

Abstract

Quantitative mass spectrometry imaging (MSI) of metals in biological tissue sections by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) using matrix-matched laboratory standards has been established previously. Here an improved calibration strategy is proposed, correcting for variable section thickness by normalization of sample and standard ion intensities to the average ¹³C⁺ ion signal of all ablated sample and standard material, respectively. Altered metal metabolism is known in Alzheimer's disease of which amyloid precursor protein (APP) transgenic mice are a popular model. Quantitative distribution analysis of Fe, Zn, Cu and Mn in horizontal brain sections of 45 week old Tg2576 transgenic mice showed a 22% decrease of Cu and changes of Fe, Zn and Mn of −1%, −7% and −17%. Local evaluation across a set of anatomically defined regions of interest showed an increased circum-ventricular to parenchyma ratio of Cu pointing to a higher Cu efflux and a heterogeneous pattern of Fe changes pointing to clearance of Fe at the sites of early pathology. Congruencies to synchrotron X-ray fluorescence data on distinct types of APP mice are discussed. MSI by LA-ICP-MS thus proved as a valuable and versatile tool for studying the cerebral metallo-architecture and the validation of animal models.