Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging

Abstract

PurposeTo evaluate the age-dependent microstructure changes in 5xFAD mice using high-resolution diffusion tensor imaging (DTI).MethodsThe 5xFAD mice at 4, 7.5, and 12 months and the wild-type controls at 4 months were scanned at 9.4T using a 3D echo-planar imaging (EPI) pulse sequence with the isotropic spatial resolution of 100 μm. The b-value was 3000 s/mm2 for all the diffusion MRI scans. The samples were also acquired with a gradient echo pulse sequence at 50 μm isotropic resolution. The microstructure changes were quantified with DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD). The conventional histology was performed to validate with MRI findings.ResultsThe FA values (p = 0.028) showed significant differences in the cortex between wild-type (WT) and 5xFAD mice at 4 months, while hippocampus, anterior commissure, corpus callosum, and fornix showed no significant differences for either FA and MD. FA values of 5xFAD mice gradually decreased in cortex (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) and fornix (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) with aging. Both FA (p = 0.029) and MD (p = 0.037) demonstrated significant differences in corpus callosum between 4 and 12 months age old. FA and MD were not significantly different in the hippocampus or anterior commissure. The age-dependent microstructure alterations were better captured by FA when compared to MD.ConclusionFA showed higher sensitivity to monitor amyloid deposition in 5xFAD mice. DTI may be utilized as a sensitive biomarker to monitor beta-amyloid progression for preclinical studies.

Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice

“…The observation of alterations in cortical connectivity between 5xFAD mice and age-matched WT mice is consistent with previous clinical and preclinical AD and TBI studies showing altered connectivity between brain regions [ 123 – 126 ]. Novel to our study was the clear genotype-related effect, with 5xFAD exhibiting reduced cortical interhemispheric connectivity, but increased strength of anterior to posterior connections compared to WT.…”

Genetic Variants of Phospholipase C-γ2 Confer Altered Microglial Phenotypes and Differential Risk for Alzheimer’s Disease

“…High-resolution T2*-weighted magnetic resonance (MR) images were acquired using a Bruker BioSpec 9.4T/30 MRI scanner outfitted with a high-sensitivity cryogenic RF surface receive-only coil (Bruker CyroProbe) as previously described (Maharjan et al, 2022). Images were acquired using a 3D gradient echo sequence with the following acquisition parameters: TR: 200 ms; TE: 10 ms; Ave: 2; Flip Angle: 45; Spatial resolution 25 μm isotropic.…”