ABSTRACT
Alzheimer’s disease (AD) is characterized by a gradual deterioration of cognition, and neuropsychiatric symptoms. The hallmarks of the disease are an accumulation of β-amyloid (Aβ) protein, forming senile plaques in specific brain areas, and tau protein phosphorylation promoting the formation and deposition of neurofibrillary tangles (NFT), leading to irreversible neuronal, synaptic, and memory loss.
Preclinical experimental models of AD that can mimic the human context of the disease, by simulating neuropathological changes and cognitive impairment, can be useful for studying the AD pathogenesis and for investigating new therapeutic drugs for improvement of current AD therapies.
This chapter reviews preclinical in-vivo and in-vitro models for AD useful for translation towards clinical trials for evaluating therapeutic agents. In-vivo animal models can be natural, genetic, or interventional models that extrapolate the neurodegenerative and behavioral changes of AD and are induced by pharmacological or chemical substances, inflammatory endotoxins, focal neurotoxic, electrolytic, or mechanical lesions in specific brain regions, intracerebral injection or infusion of amyloid peptides, or interference with brain metabolism.
In-vivo transgenic techniques provide genetically manipulated models and reproduce familial AD by transfecting with a gene encoding a mutant human amyloid precursor protein (APP).
In-vitro cell line culture models are alternatives to animals, allowing accurate and reproducible control of extracellular environments.
The AD biomarkers are assessed by biochemical estimations of enzymes and neurotransmitter levels in blood and cerebrospinal fluid.
