The isotropic fractionator provides evidence for differential loss of hippocampal neurons in two mouse models of Alzheimer's disease

Molecular Neurodegeneration

Dara L Dickstein²  Patrick R Hof²  Sam Gandy³  Peter H St George-Hyslop¹  Paul E Fraser¹  David Westaway⁵  John W Steele⁴  Hannah Brautigam² 

[1] Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medical Biophysics and Medicine (Neurology), University of Toronto, Toronto, ON, M5S 3H2, Canada;Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA;James J. Peters VA Medical Center, Bronx, NY, 10468, USA;Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY, 10065, USA;Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, T6G 2M8, Canada

关键词: Neuronal loss;    Isotropic fractionator;    Amyloid beta (Aβ);    Mouse models;    Alzheimer’s disease;   

Others  :  863298
DOI  :  10.1186/1750-1326-7-58

 received in 2012-05-02, accepted in 2012-09-18,  发布年份 2012

【 摘 要 】

Background

The accumulation of amyloid beta (Aβ) oligomers or fibrils is thought to be one of the main causes of synaptic and neuron loss, believed to underlie cognitive dysfunction in Alzheimer’s disease (AD). Neuron loss has rarely been documented in amyloid precursor protein (APP) transgenic mouse models. We investigated whether two APP mouse models characterized by different folding states of amyloid showed different neuronal densities using an accurate method of cell counting.

Findings

We examined total cell and neuronal populations in Swedish/Indiana APP mutant mice (TgCRND8) with severe Aβ pathology that includes fibrils, plaques, and oligomers, and Dutch APP mutant mice with only Aβ oligomer pathology. Using the isotropic fractionator, we found no differences from control mice in regional total cell populations in either TgCRND8 or Dutch mice. However, there were 31.8% fewer hippocampal neurons in TgCRND8 compared to controls, while no such changes were observed in Dutch mice.

Conclusions

We show that the isotropic fractionator is a convenient method for estimating neuronal content in milligram quantities of brain tissue and represents a useful tool to assess cell loss efficiently in transgenic models with different types of neuropathology. Our data support the hypothesis that TgCRND8 mice with a spectrum of Aβ plaque, fibril, and oligomer pathology exhibit neuronal loss whereas Dutch mice with only oligomers, showed no evidence for neuronal loss. This suggests that the combination of plaques, fibrils, and oligomers causes more damage to mouse hippocampal neurons than Aβ oligomers alone.

【 授权许可】

   
2012 Brautigam et al.; licensee BioMed Central Ltd.

【 图 表 】

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