Non human primate models for Alzheimer’s disease-related research and drug discovery

  title={Non human primate models for Alzheimer’s disease-related research and drug discovery},
  author={Debby Van Dam and Peter Paul de Deyn},
  journal={Expert Opinion on Drug Discovery},
  pages={187 - 200}
ABSTRACT Introduction: Pathophysiological mechanisms underlying Alzheimer’s disease (AD) remain insufficiently documented for the identification of accurate diagnostic markers and purposeful target discovery and development. Nonhuman primates (NHPs) have important translational value given their close phylogenetic relationship to humans and similar developmental paths in (neuro)anatomy, physiology, genetics, and neural functions, as well as cognition, emotion, and social behavior. Areas covered… 
18 Citations

Alzheimer’s disease: A clinical perspective and future nonhuman primate research opportunities

This perspective focuses on the value of nonhuman primate (NHP) models in bridging the molecular, circuit, and behavioral levels of analysis to better understand the complex genetic and environmental/lifestyle factors that contribute to AD pathogenesis.

Characterization of early Alzheimer’s-like pathological alterations in non-human primates with aging: a pilot study

Multiple AD-like pathological alteration in the prefrontal cortex of the older NHPs are found including tau hyperphosphorylation, increased activity of AMP-activated protein kinase (AMPK), decreased expression of protein phosphatase 2A (PP2A), impairments in mitochondrial morphology and postsynaptic densities (PSDs) formation.

Preclinical Marmoset Model for Targeting Chronic Inflammation as a Strategy to Prevent Alzheimer’s Disease

The communication between amyloidopathy and inflammation and the possibility of using nonhuman primates as a relevant animal model for preclinical AD research are described.

Modelling Alzheimer's disease: Insights from in vivo to in vitro three‐dimensional culture platforms

Two‐dimensional and three‐dimensional in vitro modelling of AD is focused on, which during the last few years has made significant breakthroughs in the areas of AD pathology and therapeutic screening, which could pave the way for the development of more accurate and comprehensive AD models in the future.

Immunotherapy to improve cognition and reduce pathological species in an Alzheimer’s disease mouse model

This study shows that acute treatment with an aβComAb can effectively improve performance in behavioral testing without reduction of amyloid plaque burden, and that peripherally administered IgG can affect levels of pathological species in the brain.

Testing the amyloid cascade hypothesis: Prevention trials in autosomal dominant Alzheimer disease.

The updated hypothesis states that anti-Aβ investigational therapies are likely to be most efficacious when initiated in the preclinical (asymptomatic) stages of AD and specifically when the disease is driven primarily by amyloid pathology.

Critical role of mitosis in spontaneous late-onset Alzheimer’s disease; from a Shugoshin 1 cohesinopathy mouse model

The Sgo1 model, the current “three-hit hypothesis” regarding LOAD development with an emphasis on critical role of prolonged mitosis in amyloid-beta accumulation, and implications for human LOAD intervention and treatment are discussed.

How does a researcher choose the best rodent model for their Alzheimer’s disease drug discovery study?

This research presents a novel approach to Alzheimer's disease research by utilizing a probabilistic approach, using a cell-based approach, called “ ‘situational awareness’”.

Molecular characterization of matrix metalloproteinase gene family across primates

The results illuminate the utilization of MMPs for the discovery of prognostic biomarkers and therapeutic targets for aging-related diseases and carry new messages on MMP classification.



Animal models in the drug discovery pipeline for Alzheimer's disease

The development and phenotyping of animal models is indeed essential in Alzheimer's disease‐related research as valid models enable the appraisal of early pathological processes – which are often not accessible in patients, and subsequent target discovery and evaluation.

Drug discovery in dementia: the role of rodent models

The implementation of a multidisciplinary approach combining valid animal models with new technologies improving biomarker profiling and early diagnosis of dementia subtypes, as well as prediction of patient-specific treatment outcome, will create new paths for improved treatment and prevention of AD.

Alzheimer's disease: old problem, new views from transgenic and viral models.

Nonhuman primate models of Alzheimer-like cerebral proteopathy.

The resistance of monkeys and apes to tauopathy and AD-related neurodegeneration, in the presence of substantial cerebral Aβ deposition, suggests that a comparative analysis of human and nonhuman primates could yield informative clues to the uniquely human predisposition to Alzheimer's disease.

Towards a transgenic model of Huntington’s disease in a non-human primate

Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys, and the data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.

Neurobiological Studies of Transmitter Systems in Aging and in Alzheimer‐Type Dementia a

Demonstration of the efficacy of new pharmacotherapies, neural grafts, and trophic factors designed to alleviate the effects of aging and disease on the human brain in nonhuman primates would have profound implications on the development of new therapies.

Genetically modified pig models for neurodegenerative disorders

A neuroanatomical overview in pigs is provided and a multiplex genome editing and preterm recloning approach is proposed by using the rapid growth of the ground‐breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT) to shorten the temporal requirement in generating multiple transgenic pigs.

Opportunities and challenges in developing relevant animal models for Alzheimer’s disease