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AbstractIntroductionOur primary goal was to examine demographic and clinicopathologic differences across an ethnoracially diverse autopsy‐confirmed cohort of Alzheimer's disease cases.MethodsA retrospective study was conducted in the Florida Autopsied Multi‐Ethnic cohort on 1625 Alzheimer's disease cases, including decedents who self‐reported as Hispanic/Latino (n = 67), black/African American (n = 19), and white/European American (n = 1539).ResultsHispanic decedents had a higher frequency of family history of cognitive impairment (58%), an earlier age at onset (median age of 70 years), longer disease duration (median of 12 years), and lower MMSE proximal to death (median of 4 points) compared with the other ethnoracial groups. Black decedents had a lower Braak tangle stage (stage V) and higher frequency of coexisting hippocampal sclerosis (21%); however, only hippocampal sclerosis differences survived adjustment for sex, age at onset, and disease duration. Neither Thal amyloid phase nor coexisting Lewy body disease differed across ethnoracial groups.DiscussionDespite a smaller sample size, Hispanics demonstrated longer disease duration with Alzheimer's disease, but not greater lifespan. Neuropathologic differences across ethnoracial groups supported differences in tau pathology distribution and coexisting hippocampal sclerosis, which may impact biomarker studies.

Introduction: Across 269 international sites, the POINT trial randomly assigned 4881 patients with minor ischemic stroke or high-risk transient ischemic attack to receive either clopidogrel at a loading dose of 600 mg on day 1 followed by 75 mg per day, plus aspirin at a dose of 50-325 mg per day or the same range of doses of aspirin alone. Dual antiplatelet therapy significantly reduced the incidence of major ischemic events, but also significantly increased the incidence of major hemorrhage. Clopidogrel is a prodrug that requires metabolism by the cytochrome P450 complex to act on the P2Y12 platelet receptor. CYP2C19 (cytochrome P450 family 2 subfamily C polypeptide 19) variants are associated with variable rates of metabolism of clopidogrel and thus pharmacogenomic effects may be clinically relevant. Methods: Genomic DNA was extracted from peripheral blood monocytes using the standard protocols. Genotyping for CYP2C19 *2, *3 and *17 alleles (rs4244285, rs4986893 and rs12248560) defines metabolizer/activator status and was performed using custom TaqMan Allelic Discrimination Assays on a QuantStudio™ 7 Flex Real-Time PCR System. Results: As of June 28, 2018, a total of 445 trial participants had DNA available for analysis. CYP2C19 allele genotyping demonstrated approximately one quarter of subjects (n=127; 28.6%) would be defined as poor or Intermediate metabolizers of clopidogrel. Conclusions: Based on targeted cytochrome P 450 genotyping, about one quarter of POINT patients have reduced clopidogrel activation. Additional genotyping is ongoing. We plan to present results assessing whether the treatment effect of clopidogrel is limited to those with CYP2C19 genotypes associated with normal drug metabolism.