Why bother using non-human primate models of cognitive disorders in translational research?

Camus, Sandrine; Ko, Wai Kin D.; Pioli, Elsa Y.; Bézard, Erwan

doi:10.1016/j.nlm.2015.06.012

Cited by 39 publications

(22 citation statements)

References 138 publications

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“…The advantages of using non-human primates to model AD include their biological proximity to humans, behavioral complexity, large brains that are favorable for imaging studies or CSF collection and a natural accumulation of Aβ that has 100% sequence homology with human Aβ[16, 19, 57]. There have been relatively few AD studies that have characterized AD pathology in great apes (chimpanzees, gorillas and orangutans) because of their long lifespan and ethical concerns of using great apes for research studies.…”

Section: Physiological Modelsmentioning

confidence: 99%

Alzheimer’s disease: experimental models and reality

2016

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Experimental models of Alzheimer’s disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in AD clinical trials thus far has been very poor. In part, this high failure rate has been related to the premature translation of highly successful results in animal models that mirror only limited aspects of AD pathology to humans. A greater understanding of the strengths and weakness of each of the various models and the use of more than one model to evaluate potential therapies would help enhance the success of therapy translation from preclinical studies to patients. In this review we summarize the pathological features and limitations of the major experimental models of AD including transgenic mice, transgenic rats, various physiological models of sporadic AD and in vitro human cell culture models.

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Section: Physiological Modelsmentioning

confidence: 99%

Alzheimer’s disease: experimental models and reality

2016

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“…With their similar genetics, anatomy, physiology, and behavioral repertoire, non-human primates (NHPs) provide the closest animal model to humans for understanding both normal functions as well as disease [66][67][68] . Emerging genetic modification techniques, including CRISPR, make generating transgenic NHPs with broad expression of Ca 2+ reporters a near possibility 69 .…”

Section: Discussionmentioning

confidence: 99%

Cortex-wide neural interfacing via transparent polymer skulls

Ghanbari

Carter

Rynes

et al. 2018

Preprint

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Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating cognition, perception and sensorimotor behaviors. Enormous progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. To fill this need, we have engineered "See-Shells" -digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>200 days) optical access to 45 mm 2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm through the See-Shells. See-Shells implanted on transgenic mice expressing genetically encoded calcium (Ca 2+ ) indicators allow tracking of neural activities from multiple, non-contiguous regions spread across millimeters of the cortex. Further, neural probes can access the brain through perforated See-Shells, either for perturbing or recording neural activity from localized brain regions simultaneously with whole cortex imaging. As See-Shells can be constructed using readily available desktop fabrication tools and modified to fit a range of skull geometries, they provide a powerful tool for investigating brain structure and function.

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“…L'utilisation de mesures identiques (ou directement comparables) à celles utilisées chez les patients est un facteur important pour améliorer la translation entre les domaines précliniques et cliniques [50]. Des mesures comportementales directement inspirées de tests utilisés en clinique humaine existent (ex.…”

Section: Modélisations Précliniques Des Pistes Pour Améliorer Les Modunclassified