PMID: 11898556Mar 20, 2002Paper

New developments in animal models of Alzheimer's disease

Current Neurology and Neuroscience Reports
C JanusD Westaway

Abstract

Alzheimer's disease (AD) is characterized by deterioration in mental function leading to dementia, deposition of amyloid plaques and neurofibrillary tangles (NFTs), and neuronal loss. The major component of plaques is the amyloid-beta peptide (A beta), whereas NFTs are assemblies of hyperphosphorylated forms of the microtubule-associated protein tau. Electron microscopy of NFTs reveals structures known as paired helical filaments (PHFs). In familial AD (FAD), mutations in three distinct genes drive A beta synthesis by favoring endoproteolytic secretase cleavages that liberate A beta from the Alzheimer beta-amyloid precursor protein (APP). This suggests that excess A beta initiates a pathogenic cascade in humans that culminates in all the pathologic and cellular hallmarks of AD. Building upon the knowledge of FAD mutations, incremental technical advances have now allowed reproduceable creation of APP transgenic mice that exhibit AD-like amyloid pathology and A beta burdens. These transgenic mouse lines also exhibit deficits in spatial reference and working memory, with immunization against A beta abrogating both AD-associated phenotypes. Besides establishing a proof of principle for A beta-directed therapies, these findings sugg...Continue Reading

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Citations

Mar 6, 2003·Mechanisms of Ageing and Development·Kristina Rhoades, Flossie Wong-Staal
Oct 3, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Athina MarkouThomas Steckler
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May 20, 2003·CNS Drugs·Christopher Janus
Oct 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ying ZhouYangping Shentu
Jan 19, 2021·Journal of Alzheimer's Disease : JAD·Daymara Mercerón-MartínezAdrian G Palacios
Apr 20, 2010·Neurochemistry International·Reza M SalekJulian L Griffin

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