Non-transgenic Animal Models of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a leading cause of progressive dementia and most common neurodegenerative disease worldwide. The prevalence rate of AD is expected to get triple by 2050. Pathological hallmarks of AD are amyloid-β containing plaques and neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated forms of the microtubule-associated protein tau. AD may be classified as early-onset (familial AD) and late-onset (sporadic AD). Familial AD occurs mostly in individuals of age 30–60 years and associated with mutations in amyloid precursor protein (APP) or presenilin (PS1 and PS2) genes, while sporadic AD mainly affects persons after 65 years of age and associated with mutations in apolipoprotein E4 isoform (apoE4) IR dysfunction, etc. Clinical interpretation of AD basically involves progressive deterioration in capabilities of memory, language, calculation, judgment, and behavior. AD is associated with disruption of mitochondrial function, calcium homeostasis, hormonal balance, and increased oxidative stress and neuroinflammation. Animal model has played a major role in defining critical disease-related mechanisms and evaluating novel therapeutic approaches in research. The sporadic form of AD itself probably involves several different etiopathogenic mechanisms. Neuroinflammation, head trauma, brain ischemia, and diabetes have been implicated as risk factors for AD.