Evaluation of Animal Models by Comparison with Human Late-Onset Alzheimer's Disease

Mol Neurobiol. 2018 Dec;55(12):9234-9250. doi: 10.1007/s12035-018-1036-6. Epub 2018 Apr 14.

Abstract

Despite many efforts to alleviate the pathological conditions of Alzheimer's disease (AD), effective therapeutic drugs have not been developed, mainly because of the lack of molecular information about AD and animal models. We observed the reciprocal regulation of AD-associated genes (AD genes) and their related functions. Upregulated AD genes were positioned in central regions in the protein-protein interaction network and were involved in inflammation and DNA repair pathways. Downregulated AD genes positioned in the periphery of the network were associated with metabolic pathways. Using these features of AD genes, we found that 5×FAD, amyloid β-injected mice, and rats in the initial phases after bilateral common carotid artery occlusion (BCCAO) exhibited patterns that were most similar to those of AD. In contrast, using differentially expressed genes from animal models, we observed that 3×Tg and animals in late phases of BCCAO were positioned close to AD genes.

Keywords: 5×FAD; Amyloid-β; BCCAO; Late-onset Alzheimer’s disease; Microarray.

Publication types

  • Comparative Study

MeSH terms

  • Age of Onset
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks
  • Humans
  • Male
  • Mice, Transgenic
  • Rats, Wistar