Inclusion of sub-group of ASPREE samples into the ADSP

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PROJECT SUMMARY The ASPREE (ASPirin in Reducing Events in the Elderly) study was a NIH funded, randomized placebo- controlled trial of daily low-dose aspirin in 19,114 healthy older individuals, completed in 2018 with longitudinal data. ASPREE recently joined the Alzheimer Disease Sequencing Project (ADSP) and transferred whole genome sequencing (WGS) data on 2,796 Non-Hispanic White (NHW) samples to the Genomics Center for Alzheimer Disease (GCAD) to be entered into the ADSP pipeline and incorporated into the Follow-up study of the ADSP (FUS). This supplement requests funds to process these 2,796 samples through GCAD. In addition, 926 high-risk, older unaffected individuals (these include 115 unaffected ApoE4/4 homozygotes >75 years, 609 unaffected ApoE3/4 carriers >85 years of age, and 202 unaffected individuals >90 years of age) have been collected as part of the ASPREE study. Of these 926 high-risk individuals, 502 have had WGS performed, and thus 424 require WGS. All high-risk individuals have been followed longitudinally and have two plasma samples collected at the participants entry and three years into the study. These individuals are of great interest as they have the potential to carry protective variants for AD. This proposal requests funds to perform WGS and plasma biomarker studies on these individuals and be incorporated into the ADSP-FUS dataset. The ASPREE program is bi-national and led in Australia by Monash University (PI McNeil), and in the US by the Berman Center for Outcomes and Clinical Research (PI Murray) and Massachusetts General Hospital/Harvard Medical School (PI Chan). Primary contact for this supplement proposal will be Dr. Paul Lacaze at Monash University, Melbourne, Australia. Specific aim 1 is adjudicate and harmonize clinical data from the two ASPREE datasets to generate high quality inferentially equivalent phenotypes and endophenotypes; Aim 2 is to conduct whole-genome sequencing of 424 high-risk, unaffected samples with longitudinal data ; Aim 3 is to perform biomarker studies on two separate plasma samples (at enrollment and at 3 year follow-up) on all 926 high-risk ASPREE samples; aim 4 is to collaborate with NIAGADS, GCAD and the Penn Neurodegeneration Genomics Center (PNGC and HIHG CGESG QC Teams in processing, storage, and delivery of final datasets to NIAGADS for public data release and aim 5 is to harmonize clinical data from newly acquired and existing FUS datasets to generate high quality inferentially equivalent phenotypes and endophenotypes.