Automated Detection of Amyloid-β-Related Cortical and Subcortical Signal Changes in a Transgenic Model of Alzheimer's Disease using High-Field MRI

Article type: Research Article

Authors: Teipel, Stefan J.^{a; c; d} | Kaza, Evangelia^e | Hadlich, Stefan^e | Bauer, Alexandra^a | Brüning, Thomas^b | Plath, Anne-Sophie^{b; c} | Krohn, Markus^{b; d} | Scheffler, Katja^b | Walker, Lary C.^f | Lotze, Martin^e | Pahnke, Jens^{b; c; d; *}

Affiliations: [a] Department of Psychiatry, University of Rostock, Rostock, Germany | [b] Neurodegeneration Research Lab (NRL), Department of Neurology, University of Rostock, Rostock, Germany | [c] German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany | [d] Interdisciplinary Faculty, Department of Aging Science and Humanities, University of Rostock, Rostock, Germany | [e] Center for Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany | [f] Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, USA

Correspondence: [*] Correspondence to: Jens Pahnke, MD, PhD, EFN, Neurodegeneration Research Lab (NRL), Department of Neurology, University Rostock, German National Center for Neurodegenerative Diseases (DZNE), Gehlsheimer Str. 20, 18147 Rostock, Germany. Tel.: +49 381 494 4700; Fax: +49 381 494 4702; Email: jens.pahnke@uni-rostock.de.

Abstract: In vivo imaging of amyloid-β (Aβ) load as a biomarker of Alzheimer's disease (AD) would be of considerable clinical relevance for the early diagnosis and monitoring of treatment effects. Here, we investigated automated quantification of in vivo T2 relaxation time as a surrogate measure of plaque load in the brains of ten AβPP/PS1 transgenic mice (age 20 weeks) using in vivo MRI acquisitions on a 7T Bruker ClinScan magnet. AβPP/PS1 mice present with rapid-onset cerebral β-amyloidosis, and were compared with eight age-matched, wild-type control mice (C57Bl/6J) that do not develop Aβ-deposition in brain. Data were analyzed with a novel automated voxel-based analysis that allowed mapping the entire brain for significant signal changes. In AβPP/PS1 mice, we found a significant decrease in T2 relaxation times in the deeper neocortical layers, caudate-putamen, thalamus, hippocampus, and cerebellum compared to wildtype controls. These changes were in line with the histological distribution of cerebral Aβ plaques and activated microglia. Grey matter density did not differ between wild-type mice and AβPP/PS1 mice, consistent with a lack of neuronal loss in histological investigations. High-field MRI with automated mapping of T2 time changes may be a useful tool for the detection of plaque load in living transgenic animals, which may become relevant for the evaluation of amyloid lowering intervention effects in future studies.

Keywords: Alzheimer's disease, amyloid-β, high-field MRI, iron deposition, transgenic mouse models, T2 relaxation time

DOI: 10.3233/JAD-2010-101035

Journal: Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 221-237, 2011