Cognitive Deficits and Alzheimer's Disease-Like Pathologies in the Aged Chinese Tree Shrew

Mol Neurobiol. 2024 Apr;61(4):1892-1906. doi: 10.1007/s12035-023-03663-7. Epub 2023 Oct 9.


Alzheimer's disease (AD) is the most common chronic progressive neurodegenerative disease in the elderly. It has an increasing prevalence and a growing health burden. One of the limitations in studying AD is the lack of animal models that show features of Alzheimer's pathogenesis. The tree shrew has a much closer genetic affinity to primates than to rodents and has great potential to be used for research into aging and AD. In this study, we aimed to investigate whether tree shrews naturally develop cognitive impairment and major AD-like pathologies with increasing age. Pole-board and novel object recognition tests were used to assess the cognitive performance of adult (about 1 year old) and aged (6 years old or older) tree shrews. The main AD-like pathologies were assessed by Western blotting, immunohistochemical staining, immunofluorescence staining, and Nissl staining. Our results showed that the aged tree shrews developed an impaired cognitive performance compared to the adult tree shrews. Moreover, the aged tree shrews exhibited several age-related phenotypes that are associated with AD, including increased levels of amyloid-β (Aβ) accumulation and phosphorylated tau protein, synaptic and neuronal loss, and reactive gliosis in the cortex and the hippocampal tissues. Our study provides further evidence that the tree shrew is a promising model for the study of aging and AD.

Keywords: Alzheimer’s disease; Amyloid accumulation; Cognitive deficits; Gliosis; Tau phosphorylation; Tree shrew.

MeSH terms

  • Aged
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Child
  • Cognition
  • Cognitive Dysfunction* / metabolism
  • Disease Models, Animal
  • Humans
  • Infant
  • Neurodegenerative Diseases*
  • Shrews / metabolism
  • Tupaia / metabolism
  • Tupaiidae / metabolism
  • tau Proteins / genetics


  • tau Proteins
  • Amyloid beta-Peptides