In response to the National Alzheimer’s Project Act (NAPA), Public Law 111-375 and NAPA Plans to Address Alzheimer’s Disease, in 2012 NIA instituted a new genetics initiative (the Alzheimer’s Disease Sequencing Project [ADSP]) to understand the genetic architecture of Alzheimer’s Disease and Related Dementias (AD/ADRD). This project involves a large number of study participants from ethnically diverse populations and will capture and analyze common and rare genetic variation.
The overarching goals of the Alzheimer’s Disease Sequencing Project (ADSP) are to:
- Identify new genes and genetic variations that contribute to increased risk for or protection against AD/ADRD
- Provide insight as to why these genes and variations impact AD/ADRD
- Identify potential avenues or approaches to transform genetic results into meaningful therapeutic targets for further development.
The ADSP requires a large number of study participants to capture all the relevant genetic variation. Using existing samples from numerous studies, the NIA has developed infrastructure including genotyping, sequencing, computational and functional analysis, and data processing and storage centers to produce high quality data and results, which will be made available to the scientific community through NIH-approved data repositories. Analyses of these data are expected to identify new genetic risk and protective variations. Both fundamental scientific discovery and leading-edge analytic approaches will be needed to achieve the research goals. The ADSP will conduct and facilitate analyses of these data to extend previous discoveries that may ultimately result in new directions for AD/ADRD therapeutics.
The samples for the ADSP are obtained from well-characterized, ethnically diverse cohorts and datasets of individuals characterized for AD/ADRD diagnoses with biospecimens (DNA and/or other biomarkers and tissues). Investigators in the ADSP will obtain the resulting data from NIAGADS DSS (the NIA Genetics of Alzheimer’s Disease Data Storage Site Data Sharing Service) including:
- Quality control checked, cleaned, and harmonized sequence and phenotype data, using a set of routine checks on sample information, phenotype, GWAS, and sequencing data. These processes are performed to ensure the data are of high quality and are ready for downstream analyses.
- Information on the study designs of the included datasets (e.g. case-control, family-based, longitudinal, and prospective cohorts).
- Descriptions of the study datasets including demographics.
Funded under several cooperative agreements and research grant awards, studies on the discovery of genes involved in AD are robustly supported by the Alzheimer’s Disease Sequencing Project. As of 2022, ADSP comprises more than 345 investigators and 62 institutions from across the globe. The ADSP aims to identify both genes that increase the risk for AD and those that confer protection, as well as to provide insight into why some people with known risk factor genes do not develop AD. The effort also aims to identify potential avenues to find therapeutic targets for AD or prevent the disease.
Beginning in 2021, several new major initiatives have been launched under the ADSP umbrella, and explore details about each effort below:
- Alzheimer’s Disease Sequencing Project Follow-Up Study 2.0 (ADSP FUS 2.0): The Diverse Population Initiative (U01)
- ADSP Functional Genomics Consortium RFA-AG-21-006: Alzheimer’s Disease Sequencing Project Functional Genomics Consortium (U01)
- ADSP Phenotype Harmonization Consortium: Harmonization of Alzheimer’s Disease and Related Dementias (AD/ADRD) Genetic, Epidemiologic, and Clinical Data to Enhance Therapeutic Target Discovery (U24 Clinical Trial Not Allowed) PAR-20-099
- ADSP Artificial Intelligence, Machine Learning, and Deep Learning Approaches: Cognitive Systems Analysis of Alzheimer’s Disease Genetic and Phenotypic Data (U01 Clinical Trial Not Allowed) (PAR-19-269)
In addition, several NIA-funded consortia, centers, and repositories help support the work of the ADSP and AD genetics research.
- Alzheimer’s Disease Genetics Consortium (ADGC)
- The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE)
- The Collaborative for Alzheimer’s Disease Research (CADRE)
- Genome Center for Alzheimer’s Disease (GCAD)
- The NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS)
- The American Genome Center (TAGC)
- National Centralized Repository for Alzheimer’s Disease and Related Dementais (NCRAD)
- The NIA Alzheimer’s Disease Family Based Study (NIA-AD FBS)
More information can be found on this website under Funded Programs, or the NIA website below: