The Alzheimer's Biomarker Consortium - Down Syndrome (ABC-DS): MOMs' Supplement -- Modification of Maternal AD Risk in DS

SCOPE OF WORK University of Kentucky (UK) The Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS) study is currently supported by the NIA and the NICHD to conduct a longitudinal study of biomarker and genetic risk for Alzheimer’s Disease (AD) in adults with Down syndrome (DS). This is a population that is at extremely high risk for developing AD, based upon the overproduction of amyloid plaque (due to the presence of the β-amyloid precursor protein (APP) on the trisomic chromosome 21). While the mean age for developing AD among adults with DS is approximately 53 years, there is considerable variability in the age of onset, ranging from prior to age 40 to over age 70. Therefore, other factors such as genetics, lifestyle, and comorbid health issues likely contribute to the age of individual AD onset. Another possible factor contributing to age of AD onset is family history, especially a maternal history of dementia, which is known to increase the risk for AD in the general population. In this administrative supplement, we propose to leverage the currently funded ABC-DS to pilot a project focusing on parents of adults with DS, allowing us to address important questions related to the potential impact of a range of maternal genetic factors on both maternal AD risk and AD risk to their DS offspring. We propose to conduct a cross-sectional study examining blood-based AD biomarkers (e.g., plasma Aβ1-42, NfL, ptau181) and genetic factors among a cohort of healthy middle-aged and senior men and women whose adult children with DS are serving as participants in the ABC-DS. We propose to enroll approximately 22 mothers and fathers (150 across the entire ABC-DS network) of current and future ABC-DS participants from the UK site over a one-year period. Participants will undergo a brief neuropsychological evaluation, complete a set of questionnaires related to family history, physical health history and mental health, and provide blood for omics and genetics analyses. UK staff will develop an IRB submission or this study, enroll participants, obtain measures and ship plasma as outlined in the study protocol.