Alzheimer’s disease (AD) is characterized by the accumulation of plaques containing ß-amyloid (Aß) and neurofibrillary tangles (NFTs) consisting of modified tau. Although Aß deposition is thought to precede the formation of NFTs in AD, the molecular steps connecting these two pathologies is not known. Previous studies have suggested that caspase activation plays an important role in promoting the pathology associated with AD. To further understand the contribution of caspases in disease progression, a triple transgenic Alzheimer’s mouse model overexpressing the anti-apoptotic protein Bcl-2 was generated. Here we show that overexpression of Bcl-2 limited caspase-9 activation and reduced the caspase cleavage of tau. Moreover, overexpression of Bcl-2 attenuated the processing of APP (amyloid precursor protein) and tau and reduced the number of NFTs and extracellular deposits of Aß associated with these animals. In addition, overexpression of Bcl-2 in 3xTg-AD mice improved place recognition memory. These findings suggest that the activation of apoptotic pathways maybe an early event in AD and contributes to the pathological processes that promote the disease mechanisms underlying AD.
This document was originally published by Society for Neuroscience in The Journal of Neuroscience. Copyright restrictions may apply. DOI: 10.1523/JNEUROSCI.5620-07.2008
Rohn, Troy T.; Vyas, Veera; Hernandez-Estrada, Tatiana; Nichol, Kathryn E.; Christie, Lori-Ann; and Head, Elizabeth. (2008). "Lack of Pathology in a Triple Transgenic Mouse Model of Alzheimer’s Disease after Overexpression of the Anti-Apoptotic Protein Bcl-2". The Journal of Neuroscience, 28(12), 3051-3059. http://dx.doi.org/10.1523/JNEUROSCI.5620-07.2008