Sex and Gender in Alzheimer’s (SAGA) Request for Applications Competition Objectives: The Sex and Gender in Alzheimer's (SAGA) request for applications aims to support scientific investigation into the contributions of sex-related biological, genetic and lifestyle to the pathophysiology of Alzheimer’s and related dementias. Background: There is no greater healthcare need than slowing or preventing Alzheimer’s disease (AD). Women are at the epicenter of the AD epidemic; two-thirds of the more than 5 million Americans living with AD are women and women account for nearly 60 percent of the more than 15 million caregivers (2014 Facts & Figures). As real a concern as breast cancer is to women’s health, women in their 60s are about twice as likely to develop AD over the rest of their lives as they are to develop breast cancer (2014 Facts & Figures). The increased incidence of AD in later life may be due to the higher longevity women generally experience; however, some evidence suggests that longevity alone may not account for the increased incidence in women in individuals’ age 60-80 years old. There may be biological underpinnings that contribute to AD pathogenesis, progression and symptom manifestation. Epidemiological and clinical studies to date have provided conflicting data regarding gender differences in incidence that may be reconciled by close examination of such biological and lifestyle variables. Sex differences affect mortality in males differentially than females, but how that affects incident dementia is not clear. For example, increased incidence in women may be linked to the higher rates of obesity, diabetes, depression and other related conditions associated with increased risk of AD. Metabolic disorders such as type-2 diabetes are often related to perimenopausal changes in females. The aging female brain undergoes irreversible changes during periomenopause, and at certain stages of life, females may experience cognitive problems. The role of hormonal disruptions in AD pathogenesis is unknown and warrants further investigation. Studies suggest sex chromosomes verses gonadal chromosomes may account for longer survival rates in animal models, yet how this translates to human studies is yet to be investigated, and how sex chromosomes (genetic, biological, etc) influence AD-like pathological changes are also undefined. There are many unanswered questions regarding the links of telomeres and other aging-related factors in females verses males that may contribute to AD. Further understanding of the biological mechanism(s) of action and the implications for disease pathogenesis of genetic differences of sex chromosomes (X and Y) as well as the potential genetic interactions related to APOEe4 and other genes are also not well understood. Lifestyle components may also have differential impact on females and males, including stress and response to stress, sleep and the presence of sleep disorders, and depression. The Sex and Gender in Alzheimer's (SAGA) requests for applications targets to address unanswered questions that will provide greater understanding of the underlying pathogenesis of Alzheimer’s and related dementias. Potential themes: SAGA is a new grant mechanism targeted to address the gaps in our understanding of the role biological sex and related genetic, biological, lifestyle and societal factors may play in increasing vulnerability for AD. In addition, there is a need to incorporate learnings from the developing biology fields to merge the expanding field of sex biology research with AD pathophysiological studies. Potential themes may include but not be limited to investigations that: Studies to investigate biological sex differences in aging and AD, including link of hormone, telomeres and other aging-related factors Studies of genetic links with APOEe4, X chromosome and other genes, including biological mechanism(s) of action, implications for disease pathogenesis Understanding sexual dimorphism in brain function, as it relates to vulnerability for AD and related dementias Investigating links between hormone levels (i.e. perimenopause) and energy metabolisms (i.e. shift from glucose to ketone energy usage) for disease pathogenesis Investigating the biological sex contributions to brain networks, pathology and link to clinical phenotypes of AD and related dementias Understanding various lifestyle factors (i.e. stress, vascular and metabolic contributions, sleep, depression) impact neurobiological context on vulnerability for AD and related dementias Investigating stress response differences between male/ female and impact on disease vulnerability as well as ways to ameliorate stress-related impact While discovery science (i.e. basic and translational studies) and human based studies of investigation are encouraged, clinical trials are not likely to be considered responsive to this RFA. General considerations and Eligibility: Researchers with full-time staff or faculty appointments (Assistant Professor and above) are encouraged to apply. Any proposal must have a clear focus on Alzheimer’s disease and related dementia and be translational in nature. All proposals should clearly and explicitly outline the measure to be investigated, the methods for study, and outcomes. Researchers from underrepresented groups are encouraged to apply. Funding and award period: The Association anticipates funding up to six SAGA awards. Each award is limited to $250,000 (direct and indirect costs) for up to three (3) years. Requests in any given year may not exceed $100,000 (direct and indirect costs). Indirect costs are capped at 10 percent (rent for laboratory/office space is expected to be covered by indirect costs paid to the institution). Eligibility: Researchers with full-time staff or faculty appointments (Assistant Professor and above) are encouraged to apply. Applications from post-doctoral candidates will not be accepted. Please note: If the applicant institution does not have an Assistant Professor Position, the letter of employment should include sufficient information to allow the Alzheimer’s Association staff to evaluate the eligibility of the applicant. Ineligibility: The Alzheimer's Association will not accept new grant applications from currently funded investigators who are delinquent in submitting required reports and other deliverables on active grants. Investigators that have previous Alzheimer’s Association awards closed as ‘Incomplete’ are not eligible to apply without exception. This policy will be strictly adhered to with no exceptions. Submission and Review Procedures: The grant submission process will follow a two stage procedure. First, applicants will submit an LOI. These LOIs will be reviewed and a select number of the top rated LOIs will be invited to submit full grant applications. The exact number of full applications invited for full submission will be determined by available funding. Both LOI and the full submissions will be reviewed based on: 1) Alignment with the research priorities as outlined in the RFA. 2) Demonstrable innovation/novelty of the proposed project (especially in the context of the PIs recently funded work). 3) Impact of project on Alzheimer’s disease and related dementia research. 4) Established investigators from other fields new to Alzheimer’s and related dementia research. 5) Evidence of methodological rigor that address the research question(s) being proposed. Deadlines and Award Timeline: Letters of Intent (LOI) must be submitted through the proposalCENTRAL on-line application system at http://proposalcentral.altum.com, the site will open Monday, November 9, 2015. Letters of intent must be received by 5:00 PM EASTERN STANDARD TIME, December 21, 2015. Letters of intent will not be accepted after this date. No exceptions will be made. For those invited to submit a full application, applications must be received by 5:00 PM EASTERN STANDARD TIME, January 27, 2016. The application materials, including the application format, templates, and instructions, will be available online at proposalCENTRAL after your LOI has been approved. Scientific and technical review will be conducted from January – April 2016. Funding decisions will be shared with applicants by April 30, 2016 Mechanism of award, reporting requirements and allowable cost: The mechanism of the award is the individual research grant. The maximum allowable duration is three years. Awardees will be required to provide sixth month milestones, and have bi-annual discussions with the Alzheimer’s Association. Annual scientific progress and financial reports are required. Continuation of the grant over the awarded duration is contingent upon the meeting scientific milestones, and upon timely receipt of scientific and financial reports. Budget: A “budget summary” for the proposed research project is required and must be submitted with the application and within the allowable page limits. However, if the application is to be awarded, a more detailed budget will be required and must be approved before the disbursement of funds. Your budget must not exceed the maximum amount of the award ($250,000). Allowable costs under this award: It is required that most of the funds awarded under this program be used for direct research support. Allowable costs under this award include: Computer equipment if used strictly for data collection Support for travel to scientific and professional meetings not to exceed $1,000 per year Additional support for travel expenses necessary to carry out research planned not to exceed $1,000 per year Salary for the principal investigator, scientific (including post-doctoral fellows) and technical staff (including interviewers, interventionists, data entry staff, technicians, and administrative support staff whose work is directly related to the funded project) Manual production/development/website, etc. Costs not allowed under this award include: Tuition Computer hardware or software for investigators Rent for laboratory/office space Construction or renovation costs Questions? Please contact [email protected] for any questions regarding this program. This program was made possible from the generous support of the Women's Alzheimer's Research Initiative (WARI)