The Alzheimer’s Strategic Fund, established in 2019, will support innovative, high risk, team science opportunities that investigate and focus on outstanding questions related to the biological underpinnings of Alzheimer’s disease (AD). In its initial call for proposals, the Fund will focus on the impact of neuroimmune function in AD through the Alzheimer’s Strategic Fund: Neuroimmune Program.
Although many advances have been made in Alzheimer’s research in recent years, the field still faces gaps in our knowledge and ability to translate basic science discoveries into effective treatments and evidence-based clinical practices for dementia care. Some of the many challenges include, but are not limited to:
- Cause(s) of the disease: How and why do specific sets of neurons in select brain structures become dysfunctional? Why is there selective vulnerability in specific brain regions and not in others? What initiates these processes and are they cell autonomous or non-cell autonomous in nature? What are key steps in the cascade of events leading to neuronal cell death? How do genetic factors interact with other factors to influence these processes
- Experimental models of disease: Considerable advances have been made in the development of cellular and animal models for AD; however, these model systems do not capture the full complexity of the human condition. This has been problematic in applying these models to predict the success of specific therapeutic interventions in individuals with AD. Are there novel technologies or approaches that recapitulate the disease progression and/or pathogenesis to support model applications?
- Early and accurate detection and diagnosis: What are the most sensitive, specific and cost-effective diagnostic procedures? What are the most sensitive, specific and cost-effective procedures for assessing change throughout the course of the disease?
- Treatment: What are the most effective and safe pharmacological treatment strategies, behavioral management techniques and combinations of therapies?
- Tool development: What are key tools and/or resources that, if developed, will benefit a broader range of scientific questions and/or studies? Tools and resources developed through this funding would be made broadly available to the scientific field.
The primary neuropathological events in AD involve abnormal expression and processing of proteins, along with activation of the immune system, including innate and adaptive immunity pathways. Immune homeostasis dysregulation and neuroinflammation are evident in the brains of individuals with AD and AD-related disorders, and may be more proximal to neuronal dysfunction and death than early brain changes, such as the aggregation and accumulation of beta amyloid or tau. In its initial call for proposals, the Alzheimer’s Strategic Fund will focus on the biological neuroimmune consequences for disease in the Alzheimer’s Strategic Fund: Neuroimmune Program. Advances in molecular biology have provided the tools needed to begin to unravel the mechanisms of immune regulation and dysregulation and develop strategies to correct this molecular damage. Although these insights into the neurobiology of the disease have generated a number of ideas, the precise etiology of the disease is still unknown.
Immune dysregulation and neuroinflammation are evident in the brains of individuals with AD and AD-related disorders and may be more proximal to neuronal dysfunction and death than early brain changes, such as the aggregation and accumulation of beta amyloid or tau. The Alzheimer’s Strategic Fund: Neuroimmune Program is a new funding mechanism targeted to address gaps in our understanding of how immune responses may impact AD and AD-related disorders. Potential themes may include, but are not limited to, studies that:
- Investigate mechanisms underlying immune dysregulation in AD associated with e.g., genetic variants, comorbidities, environmental risk factors, biological sex or history of SARS-COV2 infection.
- Augment cohort studies with additional biomarker and genetic analyses including multi-omic approaches, epigenetics and genomics; blood and cerebrospinal fluid analyte; and neuroimaging.
- Develop longitudinal characterization of immune function to understand immune system dynamics and identify biomarkers with which to measure innate or adaptive immune function that is relevant to AD.
- Develop systematic, longitudinal immunoprofiling of immune cells, both peripherally and centrally, in subjects with deep phenotypic characterization relevant to AD pathology in order to understand how systemic and brain immune functions affect one another and impact biological underpinnings.
- Explore single-cell sequencing technologies to characterize and assess comparisons between AD, other dementia and control samples.
- Transfer knowledge of immune function from other research fields (e.g. cancer, HIV, cardiovascular disease and diabetes) and apply these lessons to AD models in order to stimulate new knowledge and findings.
The maximum grant amount is $300,000, with anticipated funding ranges to be $150,000 to $300,000 depending on the project scope. No indirect costs are allowable for this funding program. The maximum project duration is 3 years, and there is no minimum timeframe. The Alzheimer’s Strategic Fund committee will evaluate projects on progress toward specific milestones; continued disbursement of funds is dependent on demonstrated progress toward key milestones.
The Neuroimmune program is open to researchers at academic institutions, as well as small companies. Both nonprofits and small for-profit organizations are eligible. Small for-profit organizations are defined as companies with 50 or fewer employees. For-profits and nonprofits must provide documentation verifying status. The Principal Investigator (PI) of the project must be a full-time faculty member or paid employee of the organization submitting the proposal. If the applicant is not a paid employee, they must demonstrate that they are part of the company and a listed employee. Applications from post-doctoral researchers will not be accepted. Investigators that have received Alzheimer’s Association funding and are currently delinquent in submitting required reports or have awards closed as “Incomplete” are not eligible to apply. For questions about eligibility, please contact the Alzheimer’s Association at firstname.lastname@example.org.
Submitting a Letter of Intent
The Letter of Intent (LOI) is a required step in the application process. LOIs must be completed online. First-time users must register and complete a professional profile to begin the LOI process. No hard copies will be accepted.
The LOI is completed through the online interactive system; you will need to complete the required sections and upload any required documents. The main section will have a limit of 10,000 characters, approximately 3 pages, and should include the information below (no figures/graphics or images are allowed):
- Brief project description, including methodology.
- Specific aims of the project.
- Innovation/novelty of the project.
- Project team.
- Plan for data sharing.
Evaluation of LOIs
All LOIs will be evaluated prior to invitation for a full proposal. Only LOIs that meet program specific guidelines and meet review criteria, including the goals of the Alzheimer’s Strategic Fund call, will be invited to submit full applications. LOIs will be reviewed by a panel of experts with special attention to:
- Demonstrable innovation/novelty of the proposed project (especially in the context of the PI/PIs and team recent work).
- Alignment with the research priorities of the RFA.
- Impact of project on AD research.
- Evidence of methodological rigor that address the research question(s) being proposed.
- While not required, priority will be given to studies that leverage interdisciplinary and/or inter-institutional teams to accomplish the proposed project in a way no one group would be able to do independently.
Feedback is not provided for LOIs that are not invited to submit a full application.
Submitting a full application
For those invited to submit a full application, additional materials will be required. Templates and instructions will be provided after LOI approval. Full applications will include:
- Executive summary — 1 page.
- Background/rationale — 1 page. Should include background and clearly defined hypothesis and/or rationale addressing why strategy is expected to be fruitful. This should also note the specific aims.
- Work plan — Up to 5 pages. Should include goals/specific aims, methods and project plan and should be organized in alignment with the milestones as outlined in the application.
- Project milestones:
- Work plan should be separated into one-year intervals with specific milestones to be accomplished within that time frame.
- Milestones should align with your overall project goals and be designed for easy progress evaluation and for clear determination on whether or not milestones have been met.
- For each milestone, indicate the relevant project aim.
- Principal investigator(s) and key personnel curriculum vitae or Biosketch — No more than 5 pages per person; there is no limit on the number of CVs to be included.
- Available resources and budget justification — 2 pages:
- Expenses that will not be allowed under this award include: Tuition for full degree programs, rent for laboratory/office space, construction or renovation costs, liability insurance, networking and communication fees, and any facilities fees and laboratory/supply costs not directly relevant to the project. If awarded, a full budget of planned expenses will be required.
- Include a list of tools/models available. (If appropriate, list critical tools and models to be used or needed in the course of the research.)
- No indirect costs will be allowed.
- Budget —Should be broken down in one-year increments and align with project milestones.
- Data sharing plan — 1 page:
- It is expected that data generated through this funding mechanism will include a robust plan for sharing data as well as appropriate included budget to accommodate this plan. Data sharing is a key component of the application and will be considered in the review and evaluation.
- Information on timelines, feasibility and the platform(s) and/or mechanisms of sharing should be included.
- Failure to share data appropriately may prevent investigators from being eligible for future funding.
- Citations/references — 1 page: Use the reference style that is most common in the major journal(s).
Deadlines and award timeline
Letters of Intent:
Open now at https://proposalcentral.com
. No hard copies will be accepted.
5 p.m. EST on Thursday, Aug. 20, 2020. Letters of intent will not be accepted after this date. No exceptions will be made. LOIs will be reviewed and moved forward on a rolling basis.
Full application deadline:
For those invited to submit a full application, the full application must be received by 5 p.m. EST, five (5) weeks from the date of invitation. Applications will not be accepted after this date. No exceptions will be made. No hard copies or emails will be accepted.
By Nov. 30, 2020
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