ADSP Overview

The Alzheimer’s Disease Sequencing Project (ADSP) was initiated in 2012 to leverage the promise of next-generation sequencing to identify genes and variants that influence either risk for or protection from Alzheimer’s Disease (AD) and AD Related Dementias (ADRD). This Project is designed to capture and analyze common and rare genetic variation across a large number of study participants from ethnically diverse populations. The ADSP also aims to identify potential avenues to find therapeutic targets for AD or prevent the disease.

Program Objectives

  1. Identify new genes involved in AD/ADRD.
  2. Identify variants contributing to increased risk for or protection against AD/ADRD.
  3. Provide insight as to why individuals with known risk factor genes have a delayed onset or escape from developing AD/ADRD.
  4. Investigate the impact of genetic admixture on AD risk, resistance, or resilience.
  5. Maximize the scientific and translational impact of the genetic discoveries by ensuring that the large-scale AD genetics data, methods, and analyses are shared rapidly and broadly.
  6. Facilitate the uptake of ADSP resources by the external research community through effective outreach and communication.
  7. Develop metrics to quantify the impact of ADSP resources on basic and translational AD/ADRD research in support of NIA’s overall strategy to enable a precision medicine approach to AD/ADRD treatment and prevention.

Research Participants

The ADSP requires a large number of study participants to enable the identification of all the relevant genetic variation. The Project draws on existing samples from well-characterized, ethnically diverse cohorts and datasets of individuals characterized for AD/ADRD diagnoses with biospecimens (DNA and/or other biomarkers and tissues).

Research Infrastructure

The NIA has developed research infrastructure including genotyping, sequencing, computational and functional analysis, and data processing and storage centers to produce high quality data and results, which are made available to the scientific community through NIH-approved data repositories.

Investigators obtain ADSP data from the 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.

Analyses of these data are expected to identify new genetic risk and protective variants. Both fundamental scientific discovery and leading-edge analytic approaches are needed to achieve the research goals. The ADSP conducts and facilitates analyses of these data to extend previous discoveries that may ultimately result in new directions for AD/ADRD therapeutics.

ADSP Investigators

Funded under several cooperative agreements and research grant awards, studies on the discovery of genes involved in AD are robustly supported by the ADSP. As of 2022, ADSP comprises more than 345 investigators and 62 institutions from across the globe.

In addition, several NIA-funded consortia, centers, and repositories help support the work of the ADSP and AD genetics research.

Consortia:

  • 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)

Infrastructure:

  • 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 DementiasDementais (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: