Alzheimer’s Disease Multimodal Atlas Projects (AD-MAPs)

Alzheimer’s disease (AD) is a progressive neurodegenerative disease of the brain and the most common form of dementia in older adults. The progression of AD often follows a predictable temporal and spatial pattern where specific brain regions are affected at different stages of the disease. However, it is unclear why the disease affects certain regions of the brain or which specific cell types within these brain regions are selectively vulnerable. To discover cell types and circuits that are altered in normal aging and AD progression, the AD-MAPs program supports efforts to generate comprehensive multimodal atlases and brain-wide connectomes across species. In addition, the AD-MAPs program supports projects performing secondary analyses of these datasets. Ultimately, the goal of the program is to enable a deeper understanding of selective cell and circuit vulnerability in aging and AD.

AD-MAPs Funding Opportunities

Explore current NIA funding opportunities related to AD-MAPs.

Concept: Data Coordinating Center for the Aging and Alzheimer’s Disease Mouse Brain Atlas (AD-MBA)

  • As part of the AD-MAPs program, NIA supports multiple projects using mouse models to generate comprehensive atlases of brain cell types and circuits that are altered during aging and dementia. Currently, there is no dedicated support for a centralized data sharing, integration, and dissemination infrastructure, and thus these valuable datasets remain siloed. This concept seeks to address this critical need by unifying these multiscale datasets and creating a central, unified research resource: The Aging and AD Mouse Brain Atlas (AD-MBA). Creation of the AD-MBA will include establishment of a data coordinating center to facilitate collaborations across groups, perform intensive analysis of multiscale datasets, and manage their dissemination. A successful coordinating center will:
    • Integrate and harmonize existing multi-modal datasets from a subset of NIA-supported studies.
    • Develop and incorporate tools for multi-scale modeling of multi-omics and connectomics datasets.
    • Create an accessible web-based platform to disseminate integrated data.
    • Capitalize on existing resources and infrastructure, including the AD Knowledge Portal, and enable future alignment with other NIH programs, such as MODEL-AD and the BRAIN Initiative .

RFA-AG-25-024: Access and Manipulation of Brain Cell Subtypes Implicated in Aging and AD/ADRD (R61/R33)

  • This Notice of Funding Opportunity (NOFO) invites applications proposing innovative strategies to target and manipulate brain cell subtypes that are altered in aging, Alzheimer's disease and Alzheimer’s disease-elated dementias (AD/ADRDs). Specifically, the goal of this NOFO is to encourage the development and utilization of sophisticated tools that pair breakthroughs in adeno-associated virus (AAV) capsid engineering with enhancer element identification to do the following:
    • Optimize precise targeting of disease-relevant cell subtypes in aged and degenerating mammalian brains.
    • Monitor and/or manipulate these cells in vivo to address mechanistic hypotheses related to brain aging and AD/ADRD in animal models.

NOT-AG-21-040: Selective Cell and Network Vulnerability in Aging and Alzheimer's Disease (R01/R21)

  • The goal of this Notice of Special Interest (NOSI) is to stimulate research to define and characterize neural cell populations (e.g., neurons and glia), neural activity and circuits, structural and functional networks, and brain regions that are vulnerable (or resistant) in brain aging and AD and the mechanisms underlying such selective vulnerability.

Projects in the AD-MAP Program

Highlighted below are a selection of ongoing grants within the AD-MAPs program.

Cellular Atlases

Advances in single cell molecular profiling technologies have enabled the discovery and characterization of brain cell types that are selectively vulnerable during normal aging and neurodegenerative disease. Using transcriptomics and epigenomics approaches, NIA supported investigators are developing high resolution brain-wide maps of cell types during aging and AD progression in mouse models and humans. By identifying impacted cell types in specific brain regions at different stages of AD, these cellular atlases will ultimately serve as a platform to further research toward understanding selectively vulnerable cell types in AD. Select NIA grants are shown below.

Human

Mouse

Circuit Connectomes

Brain network function is disrupted in many neurodegenerative disorders, including AD, and this dysregulated circuitry can lead to a progressive loss of cognitive function. Despite the impact of circuit level dysfunction in AD, there lacks a detailed characterization and mechanistic understanding of the neural circuitry contributing to disease progression. To enable a deeper understanding of brain circuits and connectivity in normal aging and AD, NIA supported investigators are generating brain-wide connectomes in mouse models and humans. Select NIA grants are shown below.

Human

Mouse

Secondary Analysis

To further characterize selectively vulnerable cells and circuits in brain aging and AD, advanced computational approaches are being leveraged to maximize the wealth of data emerging from the AD-MAPs program. Select NIA grants are shown below.

Contact Information

To learn more about NIA-funded research on Alzheimer’s Disease Multimodal Atlas Projects (AD-MAPs) contact Erin E. Gray, Ph.D. at erin.gray@nih.gov .

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