In Vivo Dynamic of Amyloid Induced Dystrophic Neurites

Principal Investigator

Project Summary


In AD, the appearance of dystrophic or degenerating neuritis, which are thought to disrupt neuronal function, correlates with the clinical severity of dementia. However, it remains unknown whether the damage to these neuronal structures is static, dynamic or possibly reversible. Dr. Brendza is analyzing neuritic plaques in the brains of living transgenic mice that develop amyloid plaques and AD-like pathology. Amyloid-associated dystrophic neurites, as well as unaffected neuron structures, can be visualized in these animals by their inherent fluorescence. Dr. Brendza is using this system to investigate whether dystrophic neurites undergo dynamic changes over time and to determine if treatments that remove amyloid will reverse the neuronal damage. It is hoped that this research will yield new insight into the dynamic nature of amyloid toxicity and help scientists understand whether removing existing amyloid or sequestering diffusible toxic forms of amyloid-beta peptide is a valid target for the treatment of Alzheimer's disease.

Publications

Brendza, R.P. and Holtzman, D.M. (2006) Amyloid-beta immunotherapies in mice and men. Alzheimer Dis. Assoc Disord. 20(2):118-123.  

Brendza, R.P., Bacskai, B.J., Cirrito, J.R., Simmons, K.A., Skoch, J.M., Klunk, W.E., Mathis, C.A., Bales, K.R., Paul, S.M., Hyman, B.T., and Holtzman, D.M. (2005) Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice. J Clin Invest. 115(2):428-433. [Alzforum Recommended Paper]  
 

First published on: June 11, 2008

Last modified on: February 25, 2024