Interpreting Disease Heterogeneity in Alzheimer’s and Parkinson’s Disease

Study Rationale:
The memory loss that is commonly associated with Alzheimer’s disease is thought to be caused by the accumulation of a protein called amyloid that disrupts the structure and function of brain cells in memory circuits. The impaired movement commonly associated with Parkinson’s disease is thought to be the product of the reduction of a chemical in the brain, known as dopamine, in the specific brain circuits that regulate movement. However, some individuals can live normal and productive lives with highly elevated levels of amyloid or very depleted levels of dopamine.

Hypothesis:
We believe the brain anatomy of some individuals demonstrates a resilience “signature” to Alzheimer’s or Parkinson’s disease that can be measured using magnetic resonance imaging (MRI) data.

Study Design:
In this project we will map the memory and motor circuits using sophisticated computer programs and new mathematical modeling techniques that describe relationships between brain structures as a network (using similar techniques used to model complex systems like the Internet or traffic on highways). We will use MRI data from thousands of individuals from publicly available databases such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Parkinson’s Progression Marker Initiative (PPMI) to better understand the architecture of the brain in healthy individuals who have high levels of amyloid or low levels of dopamine.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
Finding signatures of how the brain can stay healthy even though it may share some of the characteristics of those suffering from these diseases is critical. It will make it possible for us to better understand how older individuals can be healthy and active throughout the length of the lifespan.

Next Steps for Development:
The results from this work will provide critical information for the development of new therapies that seek to delay the onset of Alzheimer’s or Parkinson’s disease. The brain “signatures” developed through the course of our work can be used to better understand how the brain may remain resilient to these disorders that are so prevalent amongst the oldest of our populations.