Insight into the emerging and common experimental in-vivo models of Alzheimer's disease

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.

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

Fig. 1

Pathological similarities between human and rodent brain in AD. This figure shows the similarities in the pathologies of rodent brain and human brain during the progression of Alzheimer’s disease. There occurs accumulation of amyloid plaques and formation of tangles along with other hallmarks like neuroinflammation, oxidative stress and synaptic dysfunction. These similarities make the animals suitable for AD research which may aid in the development of potent therapeutics for AD

Fig. 2

Animals models and their characteristic pathological features. This figure represents various animal models described in this study along with the consequent pathologies induced by different substances. These substances are administered by various routes including intracerebroventricular, intrahippocampal, intraperitoneal and oral. These pathologies subsequently lead to the progression of Alzheimer’s disease

Fig. 3

Transgenic and emerging models of AD. There are various knock-in and knock-out models of AD which overexpress certain genes related to AD pathology. Models like PDAPP, APP23, Tg2576 and hAPP-J20 overexpress APP gene to produce increased amount of Aβ along with other pathologies. P301S model exhibits increased tau hyperphosphorylation and models including APP/PS1, 3 × Tg and 5 × FAD show various pathologies altogether comprising Aβ deposition, tau hyperphosphorylation, neuroinflammation and other pathologies. Further figure shows newly discovered models which mimic the AD associated pathologies resulting in the development of reliable model for studying the pathogenesis and therapeutics for AD. These models include oAβ25-35 model, transgenic model expressing 82-kDa ChAT, oDGal mouse and APP knock-in rat