A Review of the Current Mammalian Models of Alzheimer's Disease and Challenges That Need to Be Overcome

Int J Mol Sci. 2021 Dec 6;22(23):13168. doi: 10.3390/ijms222313168.


Alzheimer's disease (AD) is one of the looming health crises of the near future. Increasing lifespans and better medical treatment for other conditions mean that the prevalence of this disease is expected to triple by 2050. The impact of AD includes both the large toll on individuals and their families as well as a large financial cost to society. So far, we have no way to prevent, slow, or cure the disease. Current medications can only alleviate some of the symptoms temporarily. Many animal models of AD have been created, with the first transgenic mouse model in 1995. Mouse models have been beset by challenges, and no mouse model fully captures the symptomatology of AD without multiple genetic mutations and/or transgenes, some of which have never been implicated in human AD. Over 25 years later, many mouse models have been given an AD-like disease and then 'cured' in the lab, only for the treatments to fail in clinical trials. This review argues that small animal models are insufficient for modelling complex disorders such as AD. In order to find effective treatments for AD, we need to create large animal models with brains and lifespan that are closer to humans, and underlying genetics that already predispose them to AD-like phenotypes.

Keywords: Alzheimer’s disease; animal model; construct validity; gene editing; large animal model; plaques; predictive validity; tangles; transgenesis.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / therapy
  • Animals
  • Brain / pathology*
  • Disease Models, Animal*
  • Humans
  • Phenotype