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Review
. 2012:2012:319836.
doi: 10.1155/2012/319836. Epub 2011 Nov 28.

Spines, plasticity, and cognition in Alzheimer's model mice

Tara Spires-Jones  1 , Shira Knafo
Affiliations
Review

Spines, plasticity, and cognition in Alzheimer's model mice

Tara Spires-Jones et al. Neural Plast. 2012.

Abstract

The pathological hallmarks of Alzheimer's disease (AD)--widespread synaptic and neuronal loss and the pathological accumulation of amyloid-beta peptide (Aβ) in senile plaques, as well as hyperphosphorylated tau in neurofibrillary tangles--have been known for many decades, but the links between AD pathology and dementia and effective therapeutic strategies remain elusive. Transgenic mice have been developed based on rare familial forms of AD and frontotemporal dementia, allowing investigators to test in detail the structural, functional, and behavioral consequences of AD-associated pathology. Here, we review work on transgenic AD models that investigate the degeneration of dendritic spine structure, synaptic function, and cognition. Together, these data support a model of AD pathogenesis in which soluble Aβ initiates synaptic dysfunction and loss, as well as pathological changes in tau, which contribute to both synaptic and neuronal loss. These changes in synapse structure and function as well as frank synapse and neuronal loss contribute to the neural system dysfunction which causes cognitive deficits. Understanding the underpinnings of dementia in AD will be essential to develop and evaluate therapeutic approaches for this widespread and devastating disease.

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Figures

Figure 1
Figure 1
In vivo multiphoton imaging of plaques (labeled with methoxy X-O4, blue), vasculature (labeled with Texas red dextran, red), and dendrites (transgenically expressing YFP, green) in mice transgenic for mutant human APP and PS1 crossed with YFP transgenic mice allow examination of dendritic spine plasticity and loss. Low-resolution three-dimensional image stacks (a) are used to repeatedly find the same imaging sites. Higher-resolution image stacks (b) are used for spine analysis. Scale bars 100 μm (a) 10 μm (b).
See this image and copyright information in PMC

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