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Animal Models of Alzheimer’s Disease

  • Tomomi Kiyota
Protocol
Part of the Springer Protocols Handbooks book series (SPH)

Abstract

Alzheimer’s disease (AD) ranks as a leading cause of death among the progressive neurodegenerative diseases. It is the most common form of dementia found in the elderly population and is characterized by deterioration in mental function and abnormal behavior including wandering, irritability, and aggression. The anatomical features of AD are brain shrinkage caused by massive neuronal loss and dilatation of lateral ventricles. The neuropathological hallmarks include senile plaques containing deposits of amyloid-β peptide (Aβ) and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated forms of the microtubule-associated protein tau. Both Aβ and tau can be misfolded to generate their toxic forms resulting in neuroinflammation and neurodegeneration. Normally Aβ is a soluble peptide but can be misfolded to form toxic oligomeric Aβ and fibrillar Aβ, causing amyloid deposits and cerebral amyloid angiopathy (CAA). Abnormally phosphorylated tau also forms soluble toxic oligomers and insoluble NFTs intraneuronally. Since the first murine model of AD was reported one and a half decades ago, many other models have been generated by modification of transgenes that cause familial AD. These models have contributed to significant basic research and numerous therapeutic innovations to treat AD and halt disease progression. Although most of the models mirror featured aspects of AD pathogenesis such as β-amyloidosis, NFT formation, cognitive dysfunction, and/or synaptic loss, no perfect model matching human AD is currently available. In this chapter, representative animal models for AD research and their pathological and behavioral features are described.

Keywords

Alzheimer’s disease Transgenic mouse models Amyloid-β precursor protein Presenilin Amyloid-β peptides Tau pathology 

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaUSA

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