Numerous studies on human AD biomarkers have demonstrated that the cerebral Aβ deposition begins many years before other AD-associated changes. Aβ spontaneously aggregates into β-sheet structures in the form of higher-order oligomers, protofibrils, and fibrils. The deposition of Aβ and tau is spatially and temporally associated with the progression of AD.Īmyloid-β Peptide in the Pathogenesis of Alzheimer’s DiseaseĪβ was first isolated from the cerebrovascular amyloid of AD patients in 1984 (Glenner and Wong, 2012) and recognized as the main component of senile plaque. However, these pathologies do not act in isolation, and rather form a continuum (Jack et al., 2018). Longitudinal studies of biomarker changes in AD patients have demonstrated that Aβ deposition occurs first, followed by the accumulation of tau pathology (Bateman et al., 2012 Fagan et al., 2014). Neurofibrillary tangles are intraneuronal aggregates comprised of hyperphosphorylated forms of the microtubule-binding protein tau. Aβ is produced from its precursor, known as an amyloid precursor protein (APP), via sequential cleavage by the β- and γ-secretases ( Figure 1A). β-amyloid plaques are deposited extracellularly, and consist mainly of β-amyloid protein (Aβ). AD is characterized neuropathologically by two types of depositions i.e., β-amyloid plaques and neurofibrillary tangles. Most AD patients (>99%) have the sporadic form of AD, whereas very few patients (<1%) have familial AD (FAD), which is inherited in an autosomal dominant manner. More than 55 million people have dementia worldwide, and the prevalence of dementia is expected to reach 78 million people by 2030 1. Alzheimer’s disease (AD) is the most common cause of dementia (Knopman et al., 2021). Although each mouse model has its advantages and disadvantages, further research on AD pathobiology will lead to the establishment of more accurate mouse models, and accelerate the development of innovative therapeutics.ĭementia is defined clinically as a decline in memory and impaired thinking ability, which are two domains of cognition. We will also discuss other mouse models based on neuroinflammation because recent genetic studies have suggested that microglia are crucial in the pathogenesis of AD. In this review, we will summarize the advantages and limitations of various mouse models of AD, including transgenic, knock-in, and injection models based on Aβ and tau. To develop preventive, diagnostic, and therapeutic strategies for AD, it is essential to establish animal models that recapitulate the pathophysiological process of AD. ![]() The pathological hallmarks of AD are senile plaques and neurofibrillary tangles, which comprise abnormally aggregated β-amyloid peptide (Aβ) and hyperphosphorylated tau protein. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes, eventually leading to dementia.
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