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ARRA Investments in Biomarkers of Aging Research

Public Health Burden
A biomarker is a physical, biochemical, or functional measure used as an indicator of a physiological change or disease process.  Biomarkers—sometimes referred to as surrogate markers or clinical endpoints—can be used to define, diagnose, or predict disease and enable rational treatment and monitoring of disease.  Unfortunately, there is a critical lack of specific, reliable, quantifiable, and easily measured biomarkers that correlate well with early disease progression.

Identifying Biomarkers of Alzheimer’s Disease
Alzheimer’s disease is by far the most common disease of dementia in late life, but there is currently no test or procedure that can definitively diagnosis AD.  Research suggests that the brain is already loaded with markers of AD even when an individual shows no signs or only mild symptoms of dementia.  It is essential that valid and reliable biomarkers of AD be identified at the earliest stages before the most devastating symptoms of AD become irreversible.  ARRA-supported researchers are working to:
  • Determine the relationships among the clinical, cognitive, imaging, genetic, and biochemical biomarker characteristics of the early (pre-dementia) stages of AD through the NIH Alzheimer’s Disease Neuroimaging Initiative (ADNI).1
  • Identify antecedent biomarkers, which are biomarkers that can identify the risk of developing an illness, in people who are still cognitively normal but are at the earliest clinical stages of AD so that promising treatments that could potentially delay the onset or prevent progression of AD may be tested.2
Learning from Genome-Wide Analyses
Large genome-wide association studies (GWASs) of common chronic disease phenotypes provide valuable information on the genetic risk factors underlying how people age, the risk for developing complex neurological disorders, and the differences in risk among various racial groups.  ARRA funding is providing researchers with support to:
  • Assess the associations of over 900,000 genetic markers with cognitive decline among 4,140 older African Americans to identify genetic risk factors underlying cognitive decline and related conditions in this under-studied segment of the population.  This type of study is uncommon among older African Americans despite the fact that many of these conditions are heavy burdens in this population.3
  • Conduct genome-wide scans of previously collected saliva samples from approximately 13,000 participants in the Health and Retirement Study (HRS).  As a result, researchers will be able to perform multiple association studies to identify potential genetic risks and influences on a broad range of health conditions as well as social and behavioral aspects of normal aging. Researchers will also be able to better understand the environmental contexts in which genetic risk and protective factors are expressed.4
Developing Biomarker Research Tool and Resources
There are different types of biomarkers ranging from images to fluid samples. In addition,  data acquisition, sample storage, and analysis methods for biomarkers vary greatly.  As more and more biomarkers are identified, research resources and tools for maintaining information will become increasingly important.  ARRA funds are being used to design and develop new research tools and resources.  Scientists are working to:
  • Build a molecular classifier based on peripheral blood samples and imaging data from patients with dementia as a valuable tool for biomarker identification, improved patient classification, and therapy evaluation and to further our understanding of the causes and symptoms of mild cognitive impairment or neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Lewy body disease.5
  • Establish protocols for reviewing and identifying variables that measure biological and medical biomarkers for the creation of a comprehensive registry of biomarkers for public use and to help investigators develop original research that studies the impacts of medical tests, obesity, and other health factors.6
  • Collect and distribute biomarker and psychosocial data as part of the Health and Retirement Study (HRS), including physical performance measures, anthropometric measures, blood pressure, dried blood spot assays, total and HDL cholesterol, and C-reactive protein which is implicated in inflammation and inflammatory responses, among other data.  This work will enable researchers to analyze changes in these measures over time and link changes to other life circumstances and health events.7

  1. 1RC2AG036535-01 -- Amyloid Imaging, VMCI, and Analysis for ADNI -- Michael Weiner (CA)
  2. 1RC1AG035654-01 -- LC-MS/MS Analysis of CSF and Antecedent Biomarkers of AD -- David Holtzman (MO)
  3. 1RC2AG036650-01 -- Genome-Wide Association Study of Cognitive Decline Among Older African Americans -- Denis A. Evans, Jill R. Murrell, and Philip De Jager (IL)
  4. 3U01AG009740-20S1 -- HRS 2010 Data Collection Supplement -- David R. Weir (MI)
  5. 1RC1AG035610-01 -- Genetic, Genomic, and Imaging Biomarkers in Degenerative Dementia -- Giovanni Coppola (CA)
  6. 1R21AG030168-01A1 -- Creating a Biomarker Registry for Secondary Data Collections -- James W. McNally (MI)
  7. 3U01AG009740-20S1 -- HRS 2010 Data Collection Supplement -- David R. Weir (MI)

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