Determining Research Priorities

NIH receives input from many sources when setting research and funding priorities. For Alzheimer’s disease, in addition to scientific workshops, international conferences, and other interactions with the scientific community, these sources include the National Advisory Council on Aging and the Advisory Council on Alzheimer’s Research, Care, and Services, established under the 2011 National Alzheimer’s Project Act.

View a video about the 2012 NIH Alzheimer’s Disease Research Summit: Path to Treatment and Prevention:

In support of the objectives outlined in the National Plan to Address Alzheimer’s Disease, NIH convened two major meetings to help inform the dementia research agenda. In May 2012, NIH hosted the Alzheimer’s Disease Research Summit 2012: Path to Treatment and Prevention and in mid-2013, convened the Alzheimer’s Disease-Related Dementias: Research Challenges and Opportunities workshop on frontotemporal disorders and Lewy body, vascular, and mixed dementias. These meetings brought together scientists from a variety of disciplines to share insights and develop recommendations. NIH neuroscientists who specialize in Alzheimer’s disease, related dementias, and brain aging played key leadership roles in the meetings, and they continue to monitor the research landscape for knowledge gaps, opportunities, and promising new avenues of discovery.

View a video about the Alzheimer’s Disease-Related Dementias: Research Challenges and Opportunities workshop, convened in 2013:

From such meetings, smaller workshops, and other means of scientific discourse, NIH guides the field through the development of funding opportunity announcements (FOAs). These solicitations ask for proposals from the scientific community in areas of particular promise and interest to the agency, to stimulate research growth in those areas. Some FOAs have resources set aside to fund grant applications. Others do not have dedicated funding, but nevertheless send a strong signal of interest to the research community about promising or emerging areas of science. Applications for each FOA are accepted for a set period of time, and FOAs can be reissued or, if scientific priorities change, allowed to lapse. Recent Alzheimer’s-related FOAs include an initiative to support research using optogenetics, a technique that integrates genetics and optics to control the activity of individual cells, to study brain changes in aging and Alzheimer’s disease.

The bulk of NIH’s funding goes to investigator-initiated proposals—that is, proposals that are not developed in response to a specific FOA. Applications for such funding reflect the creativity and innovation of established and new investigators who seek to build on scientific advances or who offer new ways of thinking about Alzheimer’s disease research.

All grants are selected for funding through a rigorous peer-review process in which experts in the field carefully review applications for scientific merit, innovation, and likelihood of success. Competition is intense; currently, only about 20 percent of all applications to NIH are funded. However, this means that experts consider the funded research to be highly promising.

Projects funded by NIH during 2012 and the first half of 2013 are aimed at several overarching goals, outlined below.

We want to understand Alzheimer’s at its most basic level.

Understanding a disease at its most basic level is an important first step toward developing interventions to prevent, slow, halt, or reverse disease progression. A more complete understanding of Alzheimer’s at the molecular and genetic levels will help lead to discovery of new and better targets for prevention and treatment. Recent investments in this area include:

  • National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS). This web-based repository of genetic data from a variety of studies will be available to qualified investigators worldwide for use in basic science and clinical research studies. This initiative will speed the pace of discovery by providing a centralized resource through which investigators can access, study, and share their own high-quality data relevant to Alzheimer’s disease.
  • Understanding genetic risk factors. Until 2009, only one gene, APOE ɛ4, had been shown to increase the risk of late-onset Alzheimer’s disease. Since then, with the advent of genome-wide association studies (GWAS) and other high-throughput technologies, the list of known risk-factor genes has grown substantially to include PICALM, CLU, CR1, BIN1, MS4A, CD2AP, EPHA1, ABCA7, SORL1, and TREM2. In 2013, the largest GWAS ever conducted identified 11 new genes. The research—conducted by the International Genomic Alzheimer’s Project, a collaborative, international study supported in part by the NIH—strengthens evidence about the involvement of certain pathways in the disease, such as inflammation and amyloid deposition. Researchers continue to explore the roles played by these genes.
  • Dominantly Inherited Alzheimer’s Network (DIAN). This consortium of scientific investigators is working to identify, recruit, evaluate, and follow up with individuals from families with the rare early-onset, dominantly inherited form of the disease. Newly supported projects in this area aim to identify the sequence of brain changes in early-onset Alzheimer’s before symptoms appear. Understanding this process could provide insight into the more common late-onset form of the disease. NIA anticipates renewing funding for DIAN in 2014.
  • Mechanisms of Alzheimer’s. A large program project (a group of linked projects funded under the same umbrella grant) is exploring the role of the lysosomal system, which is involved in the breakdown and recycling of cellular proteins, in Alzheimer’s pathogenesis (2P01AG017617-11A1). In another study, investigators are attempting to pinpoint the mechanism through which the ApoE4 protein contributes to development of Alzheimer’s pathology (1R15AG042781-01A1).

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