%0 Journal Article
%T Neuron loss in the 5XFAD mouse model of Alzheimer¡¯s disease correlates with intraneuronal A¦Â42 accumulation and Caspase-3 activation
%A Eimer William A
%A Vassar Robert
%J Molecular Neurodegeneration
%D 2013
%I BioMed Central
%R 10.1186/1750-1326-8-2
%X Background Although the mechanism of neuron loss in Alzheimer¡¯s disease (AD) is enigmatic, it is associated with cerebral accumulation of A¦Â42. The 5XFAD mouse model of amyloid deposition expresses five familial AD (FAD) mutations that are additive in driving A¦Â42 overproduction. 5XFAD mice exhibit intraneuronal A¦Â42 accumulation at 1.5 months, amyloid deposition at 2 months, and memory deficits by 4 months of age. Results Here, we demonstrate by unbiased stereology that statistically significant neuron loss occurs by 9 months of age in 5XFAD mice. We validated two A¦Â42-selective antibodies by immunostaining 5XFAD; BACE1 /  bigenic brain sections and then used these antibodies to show that intraneuronal A¦Â42 and amyloid deposition develop in the same regions where neuron loss is observed in 5XFAD brain. In 5XFAD neuronal soma, intraneuronal A¦Â42 accumulates in puncta that co-label for Transferrin receptor and LAMP-1, indicating endosomal and lysosomal localization, respectively. In addition, in young 5XFAD brains, we observed activated Caspase-3 in the soma and proximal dendrites of intraneuronal A¦Â42-labeled neurons. In older 5XFAD brains, we found activated Caspase-3-positive punctate accumulations that co-localize with the neuronal marker class III ¦Â-tubulin, suggesting neuron loss by apoptosis. Conclusions Together, our results indicate a temporal sequence of intraneuronal A¦Â42 accumulation, Caspase-3 activation, and neuron loss that implies a potential apoptotic mechanism of neuron death in the 5XFAD mouse.
%K Intraneuronal A¦Â42
%K 5XFAD
%K Alzheimer¡¯s disease
%K Amyloid-¦Â
%K Caspase-3
%K Neuron loss
%K Apoptosis
%U http://www.molecularneurodegeneration.com/content/8/1/2