Request for Information for Neurodegenerative Research

Notice Number: NOT-ES-13-002

Key Dates
Release Date: November 5, 2012
Response Date:  November 30, 2012  

Issued by
National Institute of Environmental Health Sciences (NIEHS)


The purpose of this time-sensitive Request for Information (RFI) is to seek input from the broad neurodegenerative research community on the most important needs and promising opportunities for the advancement of environmental exposure and neurodegenerative disease research. For the purpose of this RFI, the “environment” is defined as "any factors that are non-genetic in nature." These can include environmental chemicals, pollution, and metals, alone or in combination with, biological agents, pharmaceuticals, nutritional factors, and psychosocial and behavioral stressors. This RFI is part of a planning effort to identify the most promising research advances for new or unmet needs in neurodegenerative research that have emerged over the last 5 years, and which will lead to the development of a focused set of recommendations for research priorities to be addressed over the next 5 years.


The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people in order to promote healthier lives. To continue to fulfill its mission, the NIEHS developed a new strategic plan with a set of descriptive strategic themes leading to a collection of more specific strategic goals ( . Some of the themes and goals derived from them most relevant to this RFI are:

Theme 1 - Fundamental Research: This theme investigates the basic biological processes of how our bodies function, and of the pathways and systems that are susceptible to the effects of environmental stressors. This research addresses all levels of biological organization — molecular, biochemical pathway, cellular, tissue, organ, model organism, human, and population — and builds on the knowledge from new tools and techniques that allow us to ask more in-depth questions about the effects of our environment on biological systems.

Theme 2 - Exposure Research: This theme focuses on the study of environmental exposures themselves — internal and external — not just chemical environmental pollutants, but also exposures arising from a variety of sources, such as the microbiome, infectious agents, nutritional sources, and stress. Key research needs include technology development for exposure measurement, including better biological markers, new sensor and detector tools, remote detection of exposures, more sensitive analytical methods, high-throughput predictive pharmacokinetic models, and informatics tools to improve quantitation of information on exposure from large datasets. This theme also intersects with Theme 1, since new metrics of exposures include biological effects on key pathways involved in disease pathogenesis.

The more specific strategic plan goals arising from those themes most relevant to this RFI are:

Goal 1: Identify and understand fundamental shared mechanisms or common biological pathways, e.g., inflammation, epigenetic changes, oxidative stress, mutagenesis, etc., underlying a broad range of complex diseases, in order to enable the development of applicable prevention and intervention strategies.

Goal 2: Understand individual susceptibility across the life span to chronic, complex diseases resulting from environmental factors, in basic and population-based studies, to facilitate prevention and decrease public health burden.

Goal 4: Understand how combined environmental exposures affect disease pathogenesis

This planning effort represents an effort to implement the strategic plan in the field of neurodegenerative disease, a field in which the NIEHS has a long history of support based on the following evidence. There has been evidence for decades of a link between increased exposure to agrochemicals and an increased risk for Parkinson’s Disease. More recent work has identified specific exposures along with genetic variants and mutations in human as well as animal studies to establish the link between GXE in the disease process. This was in great part due to our support of interdisciplinary research through our former CCPDER centers and our Centers for Neruodegeneration Science which enabled researchers to identify genes affected by exposure and study them in a variety of systems from human, non-human mammalian to nonmammalian. Our support of Amyotrophic Lateral Sclerosis research has also been fruitful in finding a link between genetic variability and the risk of disease from exposure. Where we have less evidence in determining a link between genetics, exposure and disease is in Alzheimer’s though early exposure along with chronic exposure to lead has been seen as a risk for AD in animal studies along with the finding that the cyanobacterial neurotoxin BMAA has been detected and quantified in autopsy brains of AD, ALS, and Huntington’s patients. Both the heavy metal and BMAA findings as well as organophosphate pesticide exposure interfering with cognition suggested the possibility of gene/environment interaction in susceptible individuals.

To facilitate continued advancement of neurodegenerative research at all levels from basic discovery to human based research and to adhere to the goals of the strategic plan, NIEHS is leading a research planning effort to identify the most promising opportunities for the field over the next 5 years. We have held a series of workshops and meetings in neurodegenerative disease that identified new and unmet research needs from research on 1) the role of genetic and especially epigenetic variability in response to exposure and disease risk, as well as 2) a more defined role for a) inflammation, b) proteinopathies and protein degradation, c) exposure susceptibility across the life span, and d) biomarkers of presymptomatic disease. This is by no means an exhaustive list of current research that was presented but it pointed to a need to develop some new concepts to move the field of neurodegenerative disease forward. However, in the current fiscally challenging budget climate it is important for us to identify opportunities for which significant, research-based effort and focus could lead to major advances in neurodegenerative research. Therefore, this planning effort will also involve input from research stakeholders to help the Institute develop a focused set of priorities for NIEHS to address over the next 5 years.

Information Requested

To aid in developing these research priorities, this RFI invites feedback from the environmental exposure-neurodegenerative research community as well as scientists in peripheral areas.  The priorities should represent cross-cutting research opportunities that have a high probability of leading to a major advance in our biologic understanding of exposure and neurodegenerative disease.  To this end, please identify and provide input on up to three high priority research efforts that if completed over the next 5 years would lead to major advances in the science. We are interested in basic, translational, and/or epidemiological research areas as well as most importantly approaches that cut across these areas. Please note that you do not need to be a neurodegenerative disease expert to respond, and we welcome input from related disciplines. 

As stated above, your input will be used by us for consideration of research priorities.  In possibly helping to structure your responses we offer the following suggestions:

Again, the above are suggestions to help you organize your response but are not intended to be so onerous that it inhibits your ability to respond.  You can be as brief as the response merits. Also, proprietary, classified, confidential, or sensitive information should not be included in your response. 

General Information

It would also be helpful if you identified the nature of your interest in neurodegenerative research (i.e. are you a biomedical researcher or other?).

If you are an investigator, please indicate your main area of research interest, including whether the focus is basic or human based research.

Please provide your name and email address.


To assure consideration, your responses must be received by November 30, 2012. Responses to this RFI must be submitted electronically using the email address provided. Responses to this RFI are voluntary. The comments collected will be analyzed and considered in planning and development of future initiatives.  Any personal identifiers will be removed when responses are compiled.  Proprietary, classified, confidential, or sensitive information should not be included in your response. 

This RFI is for planning purposes only and is not a solicitation for applications or an obligation on the part of the United States (U.S.) Government to provide support for any ideas identified in response to it.

Please send responses to Dr. Annette Kirshner at  no later than November 30, 2012.


Please direct all inquiries to:

Annette Kirshner, PhD
Program Administrator
Cellular, Organs and Systems Pathobiology Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
National Institutes of Health
U.S. Department of Health and Human Services
P.O. Box 12233 (MD K3-15)
Research Triangle Park, NC 27709-2233
Telephone:  919-541-0488
FAX:  919-541-2860

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