Abstract
Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.
Highlights
Accepted: 23 November 2021The two core pathological hallmarks of Alzheimer’s disease (AD) are extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles, resulting from the abnormal accumulation of misfolded Aβ and tau [1]
We summarize recent advances in Magnetic resonance imaging (MRI), contrast agents, and MR spectroscopy in probing the alterations in brains of AD amyloidosis animal models
Lee et al demonstrated a 35% decrease in the availability of metabotropic glutamate receptor 5 measured by Positron emission tomography (PET); a decrease in the levels of glutamate, N-acetylaspartate, and taurine; and an increase in the level of lactate by 1 H Magnetic Resonance Spectroscopy (MRS) in 5 × FAD mice compared to wild-type at 5 months-of-age [152]
Summary
The two core pathological hallmarks of Alzheimer’s disease (AD) are extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles, resulting from the abnormal accumulation of misfolded Aβ and tau [1]. Recent advances in diagnostic imaging have provided insights into the time course of AD pathology, including Aβ, tau, and neuroinflammation, in patients and in animal disease models [4,5]. Especially the most neurotoxic oligomeric Aβ, plays a crucial role in the disease pathogenesis in animal models and leads to downstream gliosis, neuronal loss, and functional and cognitive impairment [18,19]. We summarize recent advances in MRI, contrast agents, and MR spectroscopy in probing the alterations in brains of AD amyloidosis animal models. We outline the outstanding challenges and provide an outlook for further development of preclinical MR in animal models of AD amyloidosis
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