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. 2023 Dec 20:15:1296919.
doi: 10.3389/fnagi.2023.1296919. eCollection 2023.

A systematic review for the development of Alzheimer's disease in in vitro models: a focus on different inducing agents

Manisha Prajapat #  1 , Gurjeet Kaur #  1 , Gajendra Choudhary #  1 , Paras Pahwa  1 , Seema Bansal  2 , Rupa Joshi  1 , Gitika Batra  3 , Abhishek Mishra  4 , Rubal Singla  1 , Harminder Kaur  1 , Praisy K Prabha  1 , Ajay Prakash Patel  1 , Bikash Medhi  1
Affiliations

A systematic review for the development of Alzheimer's disease in in vitro models: a focus on different inducing agents

Manisha Prajapat et al. Front Aging Neurosci. .

Abstract

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease and is associated with dementia. Presently, various chemical and environmental agents are used to induce in-vitro models of Alzheimer disease to investigate the efficacy of different therapeutic drugs. We screened literature from databases such as PubMed, ScienceDirect, and Google scholar, emphasizing the diverse targeting mechanisms of neuro degeneration explored in in-vitro models. The results revealed studies in which different types of chemicals and environmental agents were used for in-vitro development of Alzheimer-targeting mechanisms of neurodegeneration. Studies using chemically induced in-vitro AD models included in this systematic review will contribute to a deeper understanding of AD. However, none of these models can reproduce all the characteristics of disease progression seen in the majority of Alzheimer's disease subtypes. Additional modifications would be required to replicate the complex conditions of human AD in an exact manner. In-vitro models of Alzheimer's disease developed using chemicals and environmental agents are instrumental in providing insights into the disease's pathophysiology; therefore, chemical-induced in-vitro AD models will continue to play vital role in future AD research. This systematic screening revealed the pivotal role of chemical-induced in-vitro AD models in advancing our understanding of AD pathophysiology and is therefore important to understand the potential of these chemicals in AD pathogenesis.

Keywords: Alzheimer’s disease; amyloid beta; in-vitro models; neurodegeneration; tau protein.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Prisma chart of this systematic review study.
Figure 2
Figure 2
Schematic representation of Alzheimer’s Disease (AD) pathology.
Figure 3
Figure 3
Schematic representation of various inducing agents involved in Alzheimer’s disease.
Figure 4
Figure 4
Illustration of various chemicals inducing Alzheimer’s pathology in in-vitro conditions. Aluminium (Al) triggers oxidative stress and neuroinflammation, contributing to beta-amyloid plaques and tau tangles. Manganese (Mn) induces mitochondrial dysfunction and neuronal damage. Lead (Pb) disrupts calcium homeostasis, promoting beta-amyloid aggregation. Streptozocin (STZ) impairs glucose metabolism, exacerbating tau pathology. Okadaic acid (OKA) activates protein phosphatases, causing hyperphosphorylation of tau. Hydrogen peroxide (H2O2) generates oxidative stress, leading to beta-amyloid accumulation. Lipopolysaccharide (LPS) induces neuroinflammation, contributing to beta-amyloid deposition and synaptic dysfunction. Common pathways include oxidative stress, neuroinflammation, and protein aggregation, while each chemical initiates specific pathways leading to neurodegeneration.
Figure 5
Figure 5
Mechanistic pathways of Alzheimer’s induction by chemical agents in in-vitro conditions. Hydroxyurea triggers DNA damage, lipopolysaccharide (LPS) induces neuroinflammation, amyloid-beta (Aβ) promotes plaque formation, L-glutamate contributes to excitotoxicity, and arsenic disrupts cellular homeostasis. Each agent elicits specific pathways leading to Alzheimer’s pathology, collectively portraying a comprehensive understanding of the diverse molecular mechanisms involved in disease onset.
Figure 6
Figure 6
Induction of Alzheimer’s disease (AD) by distinct chemical agents in an in-vitro context. Particulate matter 2.5 initiates neuroinflammation, sevoflurane disrupts synaptic function, formaldehyde promotes tau hyperphosphorylation, magnesium chloride (MgCl2) induces oxidative stress, and paraquat triggers mitochondrial dysfunction. Each agent instigates specific pathways, collectively illuminating the intricate mechanisms underlying AD pathology in response to environmental and chemical exposures.
Figure 7
Figure 7
Illustration of the induction of Alzheimer’s disease (AD) by diverse chemical agents in an in-vitro setting. Amyloid-beta contributes to plaque formation, 27-hydroxycholesterol influences cholesterol metabolism, scopolamine disrupts cholinergic signaling, aluminium (Al) and lead (Pb) trigger neurotoxicity and oxidative stress, while hypoxia induces cellular oxygen deprivation. Each chemical agent initiates specific pathways, collectively providing insights into the multifaceted mechanisms underlying AD pathology.
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