Channing Neurodegenerative Disease Research

Integrating Genetic, Biochemical and Traditional Epidemiological Approaches to Identify Neurodegenerative Disease Causes, Risk Factors and Biomarkers

Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system (e.g., spinal cord) lose function over time and ultimately die.

Neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), among others. As many as one million people in the U.S. live with PD and MS, respectively, and around 16,000 people live with ALS. These diseases have major adverse personal, social, and economic consequences because of their progressive and disabling nature.

Prevention and early detection are critical, because there are no cures, and a clinical diagnosis typically occurs after substantial and often irreversible neuronal loss, and at a time when neuroprotective interventions are probably too late to be fully effective.

Current Research

Investigators at the Channing Division of Network Medicine (CDNM) have built a comprehensive research strategy for MS, PD, and ALS to identify:

• Causes
• Risk factors (positive and negative)
• Biomarkers of susceptibility and early diagnosis

At the core of our work is a series of prospective investigations that integrate genetic, biochemical, and traditional epidemiological approaches, and an interdisciplinary team that includes basic scientists, epidemiologists, and clinical investigators.

Environmental determinants

We are investigating the environmental determinants of MS, with focus on the possible etiological role of the Epstein-Barr virus and other infections, and the protective effect of vitamin D and its variations by age, gender, and race/ethnicity. This is a collaborative effort with contributions from leading virologists, immunologists, and geneticists in the U.S. and Europe.

Drugs, diet, and lifestyle in determining PD risk

This project includes collaborations with neurobiologists and clinical investigators, and use of biological samples for the discovery of biomarkers for PD. Products of this project include:

• The design of experimental studies to find the mechanisms underlying selected epidemiological findings, most notably the possible protective effects of caffeine, anti-inflammatory drugs, and high plasma levels of urate
• Clinical studies to assess translational implications, including a randomized trial of urate elevation in individuals with early PD

Metabolomic and lipidomic markers

We investigate metabolomic and lipidomic markers for ALS, PD, and MS. These studies are based on multiple populations, including large cohorts in the U.S. and participants in multicenter randomized trials of MS in Europe.

Other projects

Other CDNM research projects include:

• Investigations on the role of the gut microbiome in the etiology of ALS and PD
• A large longitudinal study for the early identification of prodromal PD

Study populations

Study populations developed by CDNM investigators used in this research include:

• Nurses' Health Study
• Nurses' Health Study II
• Health Professionals Follow-Up Study