The goal of this FOA is to define and characterize neural cell populations (neurons and glia), neural activity and circuits, structural and functional networks, and brain regions that are vulnerable in brain aging and Alzheimer’s Disease (AD), and the mechanisms underlying such selective vulnerability. Genetic and molecular signatures of different types of neurons and glial cells across the adult lifespan, in AD compared to other dementias of aging, and in different stages of AD will implicate cell processes and pathways mediating selective vulnerability to AD. Defining cell types by physiological measures such as electrophysiology and connectivity and manipulating neural activity in circuits and networks will provide a functional index of selective vulnerability. Applications are encouraged to use new approaches to generate sophisticated data on molecular signatures of brain cells and on structure and function of brain circuits and networks. Understanding the mechanisms underlying selective vulnerability from cells to networks in AD is critical to fully define the disease process and to develop effective therapies.
Areas of research interest and opportunity include, but are not limited to:
- Identification of neural cell populations, brain regions, neural circuits and/or large scale networks (connectomes) that contribute to vulnerability in brain aging and AD.
- Comprehensive single-cell transcriptomics (e.g. RNAseq), epigenetics (e.g. chromatin remodeling, DNA methylation), and/or genomics (e.g. sequencing for somatic mutations) of neurons and glial cells in different brain regions at different ages and pathological stages of AD.
- Multidisciplinary and multiplexed technological approaches to single-cell ‘omics’, electrophysiology and connectivity for comprehensive and integrative studies of selective vulnerability to neuro- and glial-degeneration in aging and AD.
- Mechanisms underlying selective cell sensitivity to beta-amyloid, tau and other proteinopathies, including cell-to-cell spread of pathogenic proteins, and the role of proteostasis network function in selective cell and circuitry vulnerability.
- Role of cell-intrinsic versus cell non-autonomous and/or environmental factors in selective vulnerability or adaptive responses to cell or network stressors or neurodegenerative events.
- Role of differential activity and connectivity properties of neuronal populations, circuits and networks in vulnerability (or resiliency) to aging and AD.
- Characterization of the molecular, cellular, synaptic and neural circuitry mechanisms underlying brain plasticity and resilience in counteracting vulnerability to neurodegeneration in aging and AD.
Deadlines: standard dates apply
Filed Under: Funding Opportunities