The READR project recruited families assumed to be multiply affected by early-onset AD by history or autopsy across the United States. The criteria for study entry included two living siblings affected by early-onset AD, 35 years of age or older, and a third living elderly relative without cognitive impairment. We also included families with deceased affected siblings, as long as frozen brain tissue was available for affected members. Families in which participants were symptomatic, but did not meet criteria for early-onset AD, were still included with the commitment for follow‐up. Healthy controls without a family history of AD in a first‐degree relative, who were 55 years of age or older were also recruited. The clinical diagnosis of AD was required to meet established research criteria. Families were enrolled and consented and completed the following protocols either by in‐person or telephone interview and assessments. The study protocol included a family pedigree, a phlebotomy, an extensive standardized cognitive test battery assessing performance in all cognitive domains (including the Selective Reminding Test, Benton Recognition, Orientation (from MMSE), Abstract Reasoning (similarities and identities/oddities), Naming (Boston Naming Test), Verbal Fluency “CFL,” Category Fluency (animals), Repetition, Comprehension, Benton Matching, Attention, and Literacy), and a neuropsychiatric assessment. Follow‐up visits were conducted to update the family history and obtain additional clinical information on new family members who had not previously participated.