National Institute on Aging Late Onset Alzheimer’s Disease Family Based Study (NIA-LOAD FBS)

The National Institute on Aging Late Onset Alzheimer’s disease (NIA-LOAD) Family Based Study (FBS) was established in 2003 with the goal of recruiting multiplex LOAD families for genetic research. Since that time, the NIA-LOAD FBS has recruited and followed 1,353 multiplex LOAD families, with more than 8,810 assessed family members, as well as 1,030 unrelated, non-demented elderly, including non-Hispanic whites, African Americans, and Caribbean Hispanics. Today, it is widely considered the most utilized Alzheimer’s disease (AD) genetics dataset in the world, with genome-wide single nucleotide polymorphism (SNP) arrays in 5,428 individuals, whole exome sequencing in 1,484, whole genome sequencing in 928 family members and controls, and counting. The data from these families has been included in over 100 publications and has been a major contributor to the Alzheimer’s Disease Genetics Consortium (ADGC), the Alzheimer’s Disease Sequencing Project (ADSP), the International Genomics of Alzheimer’s Project (IGAP), and others.  

Fourteen years after the initial recruitment of these multiplex families, as the offspring (adult children) of the NIA-LOAD FBS probands and siblings began entering the age of greatest risk of LOAD, great efforts were made, and continue to this day, to extend recruitment within each family, to other family members and to the next generation. This "next" generation offers an ideal opportunity to provide information concerning the penetrance and heritability of the genetic variants identified not only in their families, but in other international genetic studies. 

Since most of the NIA-LOAD FBS participants are of European ancestry, a significant effort has been made to extend this genetic research to ethnically diverse, multiplex LOAD families, which will help to both evaluate the utility of current biomarkers and enable the development of novel biomarkers. The recruitment of African Americans, Mexican Americans, and Central and South Americans residing in the United States is ongoing.

In order to set the stage for functional genomic investigations, the NIA-LOAD FBS has also expanded the biospecimens collected from family members to include additional DNA, peripheral blood mononuclear cells (PBMCs), and postmortem brain tissue. Neuropathological evaluation of NIA-LOAD FBS participants has been a priority since the inception of the study. These biospecimens are centralized at the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), where they are processed, RNA sequenced, and stored for distribution to qualified researchers. 

Many years ago, the NIA-LOAD FBS started a trend of greater cooperation and sharing of clinical and genetic data among researchers and across institutions, as a means of facilitating collaborative research and expediting scientific discovery. As a result, virtually every major genetic study of LOAD has included patients and controls from the NIA-LOAD FBS dataset. With support from a NIH Genomic Community Resources (U24) agreement, the NIA-LOAD study leadership now stands poised to take this collaborative research model to the next level.