Translational Capabilities: Single cell molecular profiling (Milestone 4.L)
Support standardized, single cell molecular profiling (genomic, proteomic, metabolomic) and open-access data infrastructure to develop a single-cell atlas for the aging brain and for AD/ADRD that can be queried by data scientists as well as basic and clinical researchers. The selection of samples for single-cell profiling needs to be optimized to allow integration of molecular profiles with existing clinical and whole-tissue molecular data (from brain and peripheral tissues) generated on the same individuals to aid novel target and biomarker discovery for precision medicine.
Support the development of integrative, computational models of cellular interactions in the CNS underlying brain aging and transition to AD and ensure their rapid and wide dissemination to the research community. These efforts should include research on:
i) understanding cell-specific vulnerability to amyloid ß, tau and other pathogenic insults, and
ii) neuron-glia, glia-glia, and other inter-cellular interactions in the context of brain aging and AD/neurodegeneration.
- Launch a program to support deep single-cell molecular profiling using cells from participants from at least 6 diverse cohorts to complement whole brain and peripheral tissue molecular profiling conducted in the same participants. Provide support for adequate hosting, curation, analyses and mining of the datasets and network models via existing and/or new data sharing platforms.
- Develop links between the AD/ADRD research community and the research community supported by the BRAIN Initiative's Cell Census efforts to accelerate the development of new cell type-selective molecular genetic tools, new model systems and gene therapy-based therapeutics.
Summary of Key Accomplishments
NIA supports a large multi-component project that aims to improve AD brain tissue banking and analysis and to adapt cutting edge single cell profiling methods. These tools will be used to generate understanding of the molecular and structural progression of AD and create a high-quality, open-access dataset for the research community.
As part of the second phase of the AMP AD program, NIA supports single nucleus/single cell molecular profiling using brain samples from participants from diverse cohorts. Large-scale single cell profiling efforts are also supported through the Psych-AD and Resilience-AD programs. All data generated through these programs are being made available to the research community through the NIA-supported AD Knowledge Portal.
This information is current as of July 2022.
- Research Implementation Area
- Translational Tools, Infrastructure, and Capabilities
- In Progress
- RFA-AG-17-054: Enhancing the Target and Biomarker Discovery Efforts of the AMP AD and M2OVE-AD Consortia (R01)
- RFA-AG-18-013: Continuation of the AMP AD Target Discovery and Preclinical Validation Consortium
- RFA-AG-18-014: Limited Competition: Data Coordinating Center for the Accelerating Medicines Partnership Target Discovery and Preclinical Validation Consortium AMP AD (U24)
Research Programs and Resources
- A platform for cell type-level transcriptomic, epigenomic and spatial interrogation of Alzheimer’s disease
- Next Generation Translational Proteomics for Alzheimer’s and Related Dementias
- AMP AD 2.0 Precision Medicine Approach to Target and Biomarker Discovery