ADMC Vision

For over a decade, the Alzheimer’s Disease Metabolomics Consortium (ADMC) has brought together leaders in Alzheimer’s disease (AD) clinical and basic research to work in close collaboration with centers of excellence in metabolomics and lipidomics combined with leaders in genetics, biochemistry, engineering, and bioinformatics. This international team of researchers are addressing the complexities of neuropsychiatric conditions including Alzheimer’s disease.

Failures of Alzheimer disease (AD) clinical trials call for a research paradigm shift. The Accelerating Medicines Partnership for AD (AMP-AD) has the central goal of shortening the time between the discovery of potential drug targets and the development of new drugs for AD. Large datasets generated by the six participating consortia have identified several hundred potential targets for novel drug discovery. The next challenge is to provide deeper molecular understanding of common pathways implicated and the key enzymes, transporters and signaling molecules that are most amenable for drug discovery and lead identification.

The ADMC, as part of the AMP-AD, began to address these and other challenges by building a comprehensive metabolomics database and an Atlas for AD. Metabolomic signatures serve as a readout capturing net influences of (epi)genetic variation, protein expression, gut microbiome and environmental and lifestyle differences. As such, they can inform about disease mechanisms, progression, heterogeneity, and treatment response. Basic biochemical knowledge has impacted the medical field and provided basic tools for monitoring disease such as measures of glucose and cholesterol in diabetes and cardiovascular diseases and resulted in development of key drugs targeting these disorders. Defining metabolic trajectories of those at risk for and with AD can similarly enable drug discovery.

The consortium openly shares computational tools and datasets in NIA’s AD Knowledge Portal fostering new collaborations and partnerships, accelerating the pace of research and laying foundations for a new era of personalized health and medicine.  Our vision is a future in which AD patients receive individualized treatments based on their integrated genomic-metabolomic profiles.

 

Our approach has allowed us to:

  1. Map metabolic failures across the trajectory of disease in order to develop a biochemical roadmap for AD that can inform novel drug discovery.
  2. Stratify patient populations based on genetic-metabolic profiles.
  3. Publish the AD Atlas: A network-based data integration resource for investigating Alzheimer’s Disease, its biomarkers, and associated endophenotypes in a multi-omics context. The database can be queried by entering one or more phenotypes, genes, proteins, or metabolites and provides an interactive interface to inspect generated networks, as well as enrichment tools for downstream analyses.
  4. Connect metabolomics data to imaging, genetics and other -omics data enabling a systems approach peripheral and central metabolism

Current research priorities include:

  1. Define longitudinal metabolic signatures in blood that inform about disease and progression.
  2. Better define contribution of diet, environmental exposures, gut microbiome composition, medications and activity on brain metabolic functions and health with our sister consortium, the Alzheimer’s Gut Microbiome Project.
  3. Expand global research efforts to include Australian and  European partners allowing us to harness the power of large cohorts across the globe (e.g., AIBL, Rotterdam Study).
  4. Define metabolomic signatures for inflammation and immune-dysregulation across diseases funded by FNIH’s AMP projects (AD, PD, T2D, AIM, SCZ).  Chronic inflammation and dysregulation of immune responses are hallmarks of a variety of non-communicable age-related diseases (NCD). Inflammatory and immune-related processes are strongly interlinked with metabolic homeostasis and signaling affecting a broad spectrum of different metabolic pathways, which, in turn, are influenced by genetic and lifestyle factors.