Animal models of Alzheimer’s disease: Applications, evaluation, and perspectives

Abstract

Although great advances in elucidating the molecular basis and pathogenesis of Alzheimer’s disease (AD) have been made and multifarious novel therapeutic approaches have been developed, AD remains an incurable disease. Evidence shows that AD neuropathology occurs decades before clinical presentation. AD is divided into three stages: preclinical stage, mild cognitive impairment (MCI), and AD dementia. In the natural world, some animals, such as non-human primates (NHPs) and canines, can develop spontaneous AD-like dementia. However, most animals do not develop AD. With the development of transgenic techniques, both invertebrate and vertebrate animals have been employed to uncover the mechanisms of AD and study treatment methods. Most AD research focuses on early-onset familial AD (FAD) because FAD is associated with specific genetic mutations. However, there are no well-established late-onset sporadic AD (SAD) animal models because SAD is not directly linked to any genetic mutation, and multiple environmental factors are involved. Moreover, the widely used animal models are not able to sufficiently recapitulate the pathological events that occur in the MCI or preclinical stages. This review summarizes the common models used to study AD, from yeast to NHP models, and discusses the different applications, evaluation methods, and challenges related to AD animal models, as well as prospects for the evolution of future studies.

Convergent transcriptomic and genomic evidence supporting a dysregulation of CXCL16 and CCL5 in Alzheimer’s disease

“…Second, although we observed expression alterations of some chemokine genes in brain tissues of AD patients and the mouse models, we have not linked the expression changes to cell types and had no experimental data to discern its potential effect on cellular function of these affected cells. We also did not validate the causal role of the highlighted genes, such as CCL5 and CXCL16 , in animal models of AD [ 70 ]. Third, we only analyzed a proportion of chemokines in this study, and we could not exclude the possibility that other chemokine genes might have a prominent role in AD pathobiology.…”

Characterization of Hair Metabolome in 5xFAD Mice and Patients with Alzheimer’s Disease Using Mass Spectrometry-Based Metabolomics

“…The 5xFAD transgenic mice model, which exhibits extracellular Aβ accumulation and senile plaques, was employed in this study. As an important tool for understanding the pathogenesis of AD, many animal models are proposed . These discriminatory chemicals should be validated and evaluated in other animal models, such as a triple transgenic AD mouse model expressing amyloid plaques and neurofibrillary tangles, to confirm the possible biomarkers for AD pathogenesis.…”

“…As an important tool for understanding the pathogenesis of AD, many animal models are proposed. 49 These discriminatory chemicals should be validated and evaluated in other animal models, such as a triple transgenic AD mouse model expressing amyloid plaques and neurofibrillary tangles, to confirm the possible biomarkers for AD pathogenesis. The clinical diagnostic accuracy of the discriminatory chemicals discovered from the hair samples from the transgenic mice model for patients with AD requires further investigation and validation.…”

Iron, ferroptosis, and ischemic stroke

“…Neuroinflammation generally refers to an inflammatory response within the central nervous system (Leng & Edison, 2021), characterized by the production of pro‐inflammatory cytokines and ROS production, which is mainly generated by microglia and astrocytes (DiSabato et al, 2016). Neuroinflammation is a key pathological factor in multiple neurological diseases, including AD (Chen & Zhang, 2022), PD (Huang et al, 2022), depression (Liu et al, 2022), and cerebral IRI (Zeng et al, 2022). Besides peroxidation and excitotoxicity, neuroinflammation is also a major event of neuronal death in stroke conditions (Lo et al, 2003; Nagy & Nardai, 2017; Yan et al, 2020), and post‐ischemic inflammation is involved in pathologies of brain IRI (Eltzschig & Eckle, 2011).…”