The Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer’s Disease

Stonebarger, Gail A.; Bimonte‐Nelson, Heather A.; Urbanski, Henryk F.

doi:10.3389/fnagi.2021.734173

Cited by 22 publications

(17 citation statements)

References 65 publications

(100 reference statements)

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“…In fact, leading researchers in the field have already been working on tauopathy induction models in the rhesus monkeys (Beckman, et al 2021). Besides that, rhesus monkeys have rarely shown distinctive neuronal loss in their brains (Stonebarger, et al 2021) or rapid deterioration of cognitive functions like AD patients (Hara, et al 2012). Taking all the above into consideration, this study reveals an unexpected yet striking resemblance between our Alzheimer’s-like NHP model and Alzheimer’s patients.…”

Section: Discussionmentioning

confidence: 99%

A non-human primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau

Jiang

Wang

Luo

et al. 2022

Preprint

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Alzheimer's disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment yet. Non-human primates (NHPs) share genetic, anatomical and physiological similarities with humans, making them an ideal model for investigating the pathogenesis and therapeutics of AD. However, the applications of NHPs in AD research have been hindered by the paucity of spontaneous or induced monkey models for AD due to their long generation time, ethical considerations and technical challenges in making genetically modified monkeys. Here we developed an AD-like NHP model by overexpressing human tau in bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, and behavioral tests. We demonstrated that after hippocampal overexpression of human tau, the rhesus macaque monkeys displayed multiple pathological features of AD, including neurofibrillary tangle formation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficit, blood vessel damage and cognitive decline. This work establishes a human tau-induced AD-like NHP model that may facilitate mechanistic studies and therapeutic treatments for AD.

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Section: Discussionmentioning

confidence: 99%

A non-human primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau

Jiang

Wang

Luo

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…One way in which we may understand mechanisms driving the age-related positivity effect is through the study of nonhuman primates, who possess central (e.g., Preuss & Wise, 2021) and autonomic (e.g., Bliss-Moreau, Machado, et al, 2013) nervous systems that are largely homologous with humans in both structure and function. As nonhuman primates' neurophysiology undergoes changes that are similar to those observed in aging humans (Alexander et al, 2008;Shively et al, 2020;Stonebarger et al, 2021;Upright & Baxter, 2021), we may expect nonhuman primates to display age-related changes to affective processing that are comparable to those observed in humans. If they do not undergo such age-related changes in affective processing, then it suggests that the mechanisms of the age-related positivity effect may be human specific and not solely dependent on aging neurobiological systems that are evolutionarily conserved.…”

Section: See No Evil: Attentional Bias Towards Threat Is Diminished I...mentioning

confidence: 91%

See no evil: Attentional bias towards threat is diminished in aged monkeys

Santistevan¹,

Fiske²,

Moadab³

et al. 2022

Preprint

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Prior evidence demonstrates that relative to younger adults, older human adults exhibit attentional biases towards positive and/or away from negative socioaffective stimuli (i.e., the age-related positivity effect). Whether or not the effect is phylogenetically conserved is currently unknown and its biopsychosocial origins are debated. To address this gap, we evaluated how visual processing of socioaffective stimuli differs in aged, compared to middle-aged, rhesus monkeys (Macaca mulatta) using eye-tracking in two experimental designs that are directly comparable to those historically used for evaluating attentional biases in humans. Results of our study demonstrate that while younger rhesus possess robust attentional biases towards threatening pictures of conspecifics faces, aged animals evidence no such bias. Critically, these biases emerged only when threatening faces were paired with neutral and not ostensibly ‘positive’ faces, suggesting social context modifies the effect. Results of our study suggest evolutionarily shared mechanisms drive age-related decline in visual biases towards negative stimuli in aging across primate species.

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“…One way in which we may understand mechanisms driving the age-related positivity effect is through the study of nonhuman primates, who possess central (e.g., Preuss & Wise, 2022) and autonomic (e.g., Bliss-Moreau, Machado, & Amaral, 2013) nervous systems that are largely homologous with humans in both structure and function. As nonhuman primates’ neurophysiology undergoes changes that are similar to those observed in aging humans (Alexander et al, 2008; Shively et al, 2020; Stonebarger et al, 2021; Upright & Baxter, 2021), we may expect nonhuman primates to display age-related changes to affective processing that are comparable to those observed in humans. If they do not undergo such age-related changes in affective processing, then it suggests that the mechanisms of the age-related positivity effect may be human-specific and not solely dependent on aging neurobiological systems that are evolutionarily conserved.…”

mentioning

confidence: 92%

See no evil: Attentional bias toward threat is diminished in aged monkeys.

Santistevan,

Fiske,

Moadab

et al. 2024

Emotion

View full text Add to dashboard Cite

Prior evidence demonstrates that relative to younger adults, older human adults exhibit attentional biases toward positive and/or away from negative socioaffective stimuli (i.e., the age-related positivity effect). Whether or not the effect is phylogenetically conserved is currently unknown and its biopsychosocial origins are debated. To address this gap, we evaluated how visual processing of socioaffective stimuli differs in aged, compared to middle-aged, rhesus monkeys (Macaca mulatta) using eye tracking in two experimental designs that are directly comparable to those historically used for evaluating attentional biases in humans. Results of our study demonstrate that while younger rhesus possesses robust attentional biases toward threatening pictures of conspecifics' faces, aged animals evidence no such bias. Critically, these biases emerged only when threatening faces were paired with neutral and not ostensibly "positive" faces, suggesting social context modifies the effect. Results of our study suggest that the evolutionarily shared mechanisms drive age-related decline in visual biases toward negative stimuli in aging across primate species.

show abstract

The Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer’s Disease

Cited by 22 publications

References 65 publications

A non-human primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau

A non-human primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau

See no evil: Attentional bias towards threat is diminished in aged monkeys

See no evil: Attentional bias toward threat is diminished in aged monkeys.

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