Alzheimer's disease (AD) is defined neuropathologically by extracellular plaques composed of ?-amyloid (A?) and intracellular tangles consisting of hyperphosphorylated forms of the microtubule-associated protein tau. A? accumulation and hyperphosphorylation of tau are recognized as key events leading to full blown AD neuropathology. Here we propose to use a unique set of small molecule drugs (gamma-secretase modulators and CRFR1 antagonists) to further explore novel AD therapeutics. This application will focus on the efficacy of drugs aimed at both A?- and tau-related pathologies in AD transgenic mice. Our overarching hypothesis is combination therapy aimed to disrupt production of both A?42 and hyperphosphorylated tau will be an efficacious treatment approach for prodromal or early AD.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG047484-01A1
Application #
8771201
Study Section
Cell Death and Injury in Neurodegeneration Study Section (CDIN)
Program Officer
Refolo, Lorenzo
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093