PET Imaging in Animal Models of Alzheimer’s Disease

Abstract

The successful development and translation of PET imaging agents targeting β-amyloid plaques and hyperphosphorylated tau tangles have allowed for in vivo detection of these hallmarks of Alzheimer’s disease (AD) antemortem. Amyloid and tau PET have been incorporated into the A/T/N scheme for AD characterization and have become an integral part of ongoing clinical trials to screen patients for enrollment, prove drug action mechanisms, and monitor therapeutic effects. Meanwhile, preclinical PET imaging in animal models of AD can provide supportive information for mechanistic studies. With the recent advancement of gene editing technologies and AD animal model development, preclinical PET imaging in AD models will further facilitate our understanding of AD pathogenesis/progression and the development of novel treatments. In this study, we review the current state-of-the-art in preclinical PET imaging using animal models of AD and suggest future research directions.

Three dimensional and four dimensional live imaging to study mechanisms of progressive neurodegeneration

“…For one thing, new animal and tissue-based models of neurodegeneration that replicate the etiologies of these complex diseases are continuously in development ( 140 ), and additional work is required to make each model imaging-compatible. In particular, more work needs to be done to correlate and adapt 4D microscopy technologies to newly developed large animal and nonhuman primate models of neurodegeneration which often model many features of human pathophysiology but typically rely on 4D positron emission tomography imaging techniques that lack cellular resolution ( 1 ). Additional challenges are often encountered when identifying the ideal time course, time resolution, and fields of view to analyze a phenotype of interest, especially in neurodegenerative disease models where tissues typically require maturity or aging for degeneration to occur.…”

“…However, these static images often fail to capture the context of the slow time course and the heterogeneity of structural and functional changes leading to degeneration. Recent advances in positron emission tomography (reviewed in ( 1 )) and functional magnetic resonance ( 2 , 3 , 4 , 5 ) have facilitated monitoring of the development and progression of neurodegenerative disease across prolonged timescales with much success, though without cellular resolution. Other recent technological advances in cellular microscopy imaging methods are now enabling scientists to monitor neurons in 3-dimensions (3D) and over prolonged time courses, providing 4-dimensional (4D) analysis to better capture the time-dependence and spatial context of neurodegenerative disease at a cellular level.…”

Moderate ethanol exposure reduces astrocyte-induced neuroinflammatorysignaling and cognitive decline in presymptomatic APP/PS1 mice

“…The uorodeoxyglucose-positron emission tomography (FDG-PET) measures glucose metabolism and brain activity [51]. Thus, we performed the micro-PET experiments using the 18 F-FDG radiotracer to examine whether MEE alters brain activity.…”

Multi-organ comparison and quantification parameters of [18F]THK-5317 uptake in preclinical mouse models of tau pathology

“…Among the non-invasive imaging modalities, especially positron emission tomography (PET), utilizing radiolabeled compounds (radiotracers) offers considerable versatility in studying diseases from multiple perspectives and at different disease stages. Despite numerous species differences between rodents and humans, PET studies usually enable a high degree of translatability as many correlative and longitudinal study designs utilized in basic research can be modified to match current clinical safety requirements with reasonable effort [5][6][7][8].…”