AbstractBackgroundThe ancestral genetic heterogeneity (admixture) of Caribbean Hispanics makes studies of this population critical to discovering ancestry‐specific genetic factors in Alzheimer's disease. As part of the Puerto Rican Alzheimer Disease Initiative (PRADI), we ascertained 80+ multigenerational families with multiple AD family members and reported linkage to 9p21. Here we present the clinical phenotype of the largest 9p21 linked family.MethodThe 18 members of this family were screened using neuropsychological test (e.g., CDR, 3MS), history of medical conditions, Apolipoprotein e4 were obtained and AD diagnosis was done by a panel of experts. Results were reported as frequencies and percentage and the associations were determined using Chi‐square.ResultThe family consisted of 17 participating family members, 76% females, a mean age of 70 years (SD=14 years). 1 participant was diagnosed with Parkinson’s disease, 6 with AD possible diagnosis, 1 as MCI and 6 were cognitively normal. No known causal genes for AD were observed through whole genome sequencing. The prevalence for APOE genotypes, 2/2, 2/3, 2/4 and 3/3, were 6%, 47%, 6% and 41% respectively. None of the AD cases in the family had an APOE4 allele. The average age of onset of AD cases was 79 years (SD=12 years) with a minimum of 60 years and maximum of 90 years. The average 3MS score for the cases was 49/100 (SD=33) and 90/100 (SD=4) for controls. CDR scores for all controls were 0 and between 2 and 1 for all cases. Depression was present in 33% of the participants, 22% diagnosed with diabetes, 25% with high cholesterol and 44% with hypertension.ConclusionIn this family, 8 individuals had neurodegenerative disorders, 5 of which had at least 1 APOE2 allele. The only APOE4 carrier is a unaffected participant (APOE 2/4) whose age at exam was 57 years. This supports a novel AD risk factor segregating in this family. Pedigree studies remain a useful tool to help unravel the pathophysiologic pathways involved in neurodegeneration.