Can MRI T1 be used to detect early changes in 5xFAD Alzheimer’s mouse brain?

Abstract

ObjectivesIn the present study, we have tested whether MRI T1 relaxation time is a sensitive marker to detect early stages of amyloidosis and gliosis in the young 5xFAD transgenic mouse, a well-established animal model for Alzheimer’s disease.Materials and methods5xFAD and wild-type mice were imaged in a 4.7 T Varian horizontal bore MRI system to generate T1 quantitative maps using the spin-echo multi-slice sequence. Following immunostaining for glial fibrillary acidic protein, Iba-1, and amyloid-β, T1 and area fraction of staining were quantified in the posterior parietal and primary somatosensory cortex and corpus callosum.ResultsIn comparison with age-matched wild-type mice, we observed first signs of amyloidosis in 2.5-month-old 5xFAD mice, and development of gliosis in 5-month-old 5xFAD mice. In contrast, MRI T1 relaxation times of young, i.e., 2.5- and 5-month-old, 5xFAD mice were not significantly different to those of age-matched wild-type controls. Furthermore, although disease progression was detectable by increased amyloid-β load in the brain of 5-month-old 5xFAD mice compared with 2.5-month-old 5xFAD mice, MRI T1 relaxation time did not change.ConclusionsIn summary, our data suggest that MRI T1 relaxation time is neither a sensitive measure of disease onset nor progression at early stages in the 5xFAD mouse transgenic mouse model.

Effects of Caloric Restriction on Spatial Object Recognition Memory, Hippocampal Neuron Loss and Neuroinflammation in Aged Rats

“…Interestingly, the dietary intervention had a significant, moderate mitigating effect on inflammatory expression, as the CR partially reversed neuroinflammation in the old animals. Other studies have also revealed a significant increase in hippocampal inflammation during aging [ 22 , 50 , 70 ], demonstrating that CR might attenuate markers of neuroinflammation and plasma cytokines [ 71 ]. This attenuation of microglial activation might dampen the release of pro-inflammatory cytokines, helping to prevent neural loss and the impairment of cognitive performance during aging [ 72 , 73 ].…”

“…In addition, microglia with a neurotoxic phenotype are considered to participate in the phagocytosis of new-born neurons that fail to integrate into existing circuits, regulating glutamatergic receptor maturation and synaptic transmission, and supporting synaptic pruning [ 21 ]. In line with this, the macrophage/microglial ionized calcium-binding adaptor 1 (Iba-1) marker was significantly elevated in the HPC of aged animals compared to adults [ 22 ].…”

Neuroimaging of Mouse Models of Alzheimer’s Disease

“…Spencer and colleagues used multimodal MRI to develop diagnostic markers of AD [ 65 , 73 ]. T1WI and T2WI, alongside histological staining, in 11-month-old 5xFAD mice revealed lower T1 relaxation times (s) in male/female 5xFAD mice.…”

“…They then tested the hypothesis that T1 relaxation times could be used as a sensitive marker to detect Aβ load at early stages. However, T1 values were not significantly different between WT and 5xFAD at younger ages (2.5- and 5-month-old) prior to the onset of robust Aβ deposition [ 73 ]. At 11 months of age, there were no significant differences between WT and 5xFAD T2 values [ 65 ].…”