The National Institute on Aging Late Onset Alzheimer’s Disease Family Based Study: A Critical Component of the International Effort to Understand Alzheimer’s Disease

ABSTRACT INTRODUCTION The National Institute on Aging Late-Onset Alzheimer’s Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of Alzheimer’s disease (AD). METHODS Recruitment focused on families with two living affected siblings and a third first degree relative similar in age with or without dementia. Uniform assessments were completed, DNA was obtained as was neuropathology, when possible. APOE genotypes, genome-wide SNP arrays and sequencing was completed in the majority of families. RESULTS A wide range in the age-at-onset in many large families was related to APOE genotype, but not in all. Variants typically associated with early-onset AD and frontotemporal dementia were also found. DISCUSSION The NIA-LOAD FBS is the largest collection of familial AD worldwide, and data or samples have been included in 126 publications addressing the genetic etiology of AD. Genetic heterogeneity and variability in the age-at-onset provides opportunities to investigate the complexity of familial AD.