Neurodegenerative Diseases

Background

Alzheimer’s disease and frontotemporal dementia belong to a diverse group of age-related neurodegenerative diseases, called tauopathies, distinguished by the appearance of neurofibrillary tangles (NFTs) in specific regions of the brain. Both diseases are progressive and ultimately fatal. No effective treatments currently exist for either of these conditions. Each disease presents a specifc pathology:

• In Alzheimer’s disease, the most common form of dementia, NFTs develop in the presence of amyloid beta senile plaques. The disease causes degeneration of the limibic and association cortices, sparing the motor and sensory regions.
• In frontotemporal dementia, degeneration is in the lobar region.

Approach

Our goal is to uncover key differences in cytokine and phospho-protein signaling between healthy and diseased brains that can be used to identify new therapeutic targets for these diseases. We are employing experimental and computational techniques from systems biology to this end:

• Our experimental approach is use primarily high-throughput Luminex screening to simultaneously measure a large number of analytes from human tissue and mouse models for each disease.
• Because there is inherently a large amount of variability between samples, we are applying computational modeling approaches from systems biology to identity important variation that distinguishes between diseased and healthy tissues, and points to new therapeutic targets.