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Neuromol Med (2011) 13:117137 DOI 10.1007/s12017-010-8141-7
REVIEW PAPER
APP Transgenic Mice: Their Use and Limitations
Claudia Balducci Gianluigi Forloni
Received: 5 August 2010 / Accepted: 20 November 2010 / Published online: 9 December 2010 Springer Science+Business Media, LLC 2010
Abstract Alzheimers disease is the most widespread form of dementia. Its histopathological hallmarks include vascular and extracellular b-amyloid (Ab) deposition and intraneuronal neurobrillary tangles (NFTs). Gradual decline of cognitive functions linked to progressive synaptic loss makes patients unable to store new information in the earlier stages of the pathology, later becoming completely dependent because they are unable to do even elementary daily life actions. Although more than a hundred years have passed since Alois Alzheimer described the rst case of AD, and despite many years of intense research, there are still many crucial points to be discovered in the neuropathological pathway. The development of transgenic mouse models engineered with overexpression of the amyloid precursor protein carrying familial AD mutations has been extremely useful. Transgenic mice present the hallmarks of the pathology, and histological and behavioural examination supports the amyloid hypothesis. As in human AD, extracellular Ab deposits surrounded by activated astrocytes and microglia are typical features, together with synaptic and cognitive defects. Although animal models have been widely used, they are still being continuously developed in order to recapitulate some missing aspects of the disease. For instance, AD therapeutic agents tested in transgenic mice gave encouraging results which, however, were very disappointing in clinical trials. Neuronal cell death and NFTs typical of AD are much harder to replicate in these mice, which thus offer a
fundamental but still imperfect tool for understanding and solving dementia pathology.
Keywords Alzheimers disease Transgenic mice
Beta-amyloid Cognitive function Synaptic plasticity
Brain imaging
Introduction
Alzheimers disease (AD) is a subtle neurodegenerative disorder affecting more than 35 million people worldwide and is expected to increase over the years (Mucke 2009). AD is symptomatically characterized by an irreversible deterioration of intellect, memory, cognition, behaviour and emotion. Affected people live three to nine years after diagnosis of probable disease; denitive diagnosis is possible only at autopsy. Most AD cases are sporadic with unknown causes, whereas the familial or inherited form of AD, accounting for only 110% of cases, presents several autosomal dominant mutations affecting...