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Lifespan diffusion MRI reveals regional abnormalities in the 5xFAD model of Alzheimer’s disease
Author(s) -
Jullienne Amandine,
Lee Jeong Bin,
Yassa Michael A.,
Territo Paul R,
Obenaus Andre,
Consortium MODELAD
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043355
Subject(s) - diffusion mri , fractional anisotropy , white matter , magnetic resonance imaging , pathology , subiculum , statistical parametric mapping , neuroimaging , hippocampus , neuroscience , medicine , biology , radiology , dentate gyrus
Background The Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium has been established to develop the next generation of Alzheimer’s disease (AD) models based on human data. We undertook lifespan diffusion magnetic resonance imaging (dMRI) to fully characterize the temporal alterations in brain structure and circuits in 5xFAD. Method All 5xFAD mice are compared to age‐matched littermates (C57BL/6J, WT) at 4, 8, and 12mo. Mice underwent high resolution diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) at 9.4T (5 B0, 30 directions b=3000 mm 2 /sec) to assess regional white and gray matter. Regional tissue features were extracted from fractional anisotropy (FA), radial (RD), axial (AD) and mean (MD) diffusivity parametric maps. Tractography was performed based on the AMBMC mouse atlas. 18F‐AV45 PET was performed to quantitate amyloid β (Aβ) load. Histology and immunohistochemical analyses verified neuroimaging findings. Result Our preliminary results focus on CA1 and the subiculum of the hippocampus and show tract differences between WT and 5xFAD females at 8 months of age. DTI metrics in these tracts are also affected by sex and genotype. For example, FA is decreased by ∼30% in 5xFAD females compared to WT females at 8 months. AV45‐PET were able to detect increasing Aβ plaque load with age in 8‐12mo old 5xFAD mice when compared to WT and was verified by immunohistochemistry. Conclusion Phenotyping of mouse models using dMRI can identify altered brain connectivity and regional tissue features. The data support that increasing Aβ deposition results in altered dMRI metrics that can be readily translated to the clinic.