Lab Anim Res.  2023 Dec;39(4):269-286. 10.1186/s42826-023-00184-1.

Insight into the emerging and common experimental in‑vivo models of Alzheimer’s disease

• Dhapola R
• Kumari S
• Sharma P
• HariKrishnaReddy D

• KMID: 2554150
• DOI: http://doi.org/10.1186/s42826-023-00184-1

Abstract

Alzheimer’s disease (AD) is a multifactorial, rapidly progressing neurodegenerative disorder. As the exact cause of the disease is still unclear, the drug development is very challenging. This review encompasses the commonly used AD models involving various chemicals, heavy metals and endogenous substances induced models and the transgenic models. It also provides insight into the reliable emerging models of AD that may overcome the shortcomings associated with available models. Chemicals like streptozotocin, scopolamine, colchicine and okadaic acid render the animal susceptible to neuroinflammation and oxidative stress induced neurodegeneration along with amyloid-β deposition and tau hyperphosphorylation. Similarly, endogenous substances like acrolein and amyloid-β 1–42 are efficient in inducing the major pathologies of AD. Heavy metals like aluminum and fluoride and mixture of these have been reported to induce neurotoxicity therefore are used as animal models for AD. Transgenic models developed as a result of knock-in or knock-out of certain genes associated with AD including PDAPP, APP23, Tg2576, APP/PS1, 3 × Tg and 5 × FAD have also been incorporated in this study. Further, emerging and advanced pathomimetic models of AD are provided particular interest here which will add on to the current knowledge of animal models and may aid in the drug development process and deepen our understanding related to AD pathogenesis. These newly discovered models include oAβ25-35 model, transgenic model expressing 82-kDa ChAT, oDGal mouse and APP knock-in rat. This study may aid in the selection of suitable model for development of novel potent therapeutics and for exploring detailed pathogenic mechanism of AD.

Keyword

Alzheimer’s disease; Animal models; STZ model; Aβ model; APP/PS1; 5 × FAD; Transgenic models; oDGal; APP knock-in