Overexpression of Bcl-2 in APP Transgenic Mice Reduces Amyloid Pathology
Abstract
Background: A growing body of evidence demonstrates caspase activation in the Alzheimer disease brain. Previously, we found that caspases play a critical role in the initiation and progression of AD pathology. The results suggest that caspase cleavage of tau is a critical step linking amyloid deposition with neurofibrillary tangle formation. Overexpression of the anti-apoptotic protein, Bcl-2 in the 3xTg-AD mouse model attenuated APP processing and subsequent tangle pathology further supporting this notion. A reduction in pathology corresponded to improved memory retention in the 3xTg-AD mice.
Methods: The current study aimed to test whether Bcl-2 overexpression in transgenic mice with only amyloid pathology exhibited similar benefits.
Results: In TgCRND8 mice, Bcl-2 overexpression decreased plaque pathology and reduce Abeta42 levels in the hippocampus.
Conclusions: These findings further implicate apoptotic mechanisms in the development of AD pathology and suggest that therapeutics targeting apoptotic pathways may prove beneficial in treating AD.