Modeling an Anti-amyloid Therapy in a Mouse Model of Alzheimer's Disease

Principal Investigator: Alena Savonenko MD, PhD

Transgenic mouse models of amyloidosis can be used to examine the impact of treatment associated with varying levels of amyloid deposition. This project uses TetOffAPP mice in which the expression of mutant amyloid precursor protein (APP) is controlled by a tetracycline-regulated promoter. A-beta production can be suppressed in these mice with doxycycline. The goal of this project is: (1) To determine if the cognitive impairments observed in these mouse models be reversed with suppression of A-beta generation. (2) To determine whether recovery of synaptic damage is associated with cognitive improvement after A-beta production is reduced. (3) Aim 3: To examine the role of monoamine systems in relation to the degree of cognitive recovery observed after reduction of A-beta production. Collectively, outcomes from these studies will address an important issue regarding the value of an anti-amyloid therapeutic strategy for AD by assessing the magnitude of functional repair and recovery after synaptic damage by A-beta.

For more information, contact Alena Savonenko at asavone1@jhmi.edu.
 

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