Automated detection of amyloid-β-related cortical and subcortical signal changes in a transgenic model of Alzheimer's disease using high-field MRI.
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.
Department of Psychiatry, University of Rostock, Rostock, Germany.
Stefan J
SJ
Teipel
Evangelia
E
Kaza
Stefan
S
Hadlich
Alexandra
A
Bauer
Thomas
T
Brüning
Anne-Sophie
AS
Plath
Markus
M
Krohn
Katja
K
Scheffler
Lary C
LC
Walker
Martin
M
Lotze
Jens
J
Pahnke
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor