Biomarker and Neurogenetics Core

Biomarker and Genetics Core, Abstract: The Biomarker and Neurogenetics Core (BNGC) of the University of Pittsburgh, Alzheimer’s Disease Research Center (PITT-ADRC) and its faculty has a long-standing history of collection of biospecimens, beginning in 1994, and advancement of genetic and biomarker discovery in Alzheimer’s disease and related diseases (ADRDs). In addition to collecting blood samples from PITT-ADRC participants, we collect and bank blood samples from non-ADRC ancillary studies that provide additional well- characterized older controls essential for our work and endophenotype data that would help to identify novel genes and biomarkers for dementia. Over the last three decades, we have accumulated DNA and plasma samples along with endophenotype and biomarker data from approximately 13,000 ADRC and non-ADRC participants. The recent development of high performances plasma biomarkers as the potential next generation of ADRD diagnostics for monitoring amyloid-beta plaque (Aβ; A) and tau neurofibrillary tangles (T) pathologies as well as neurodegeneration (N), has become a new focus of the BNGC during the last three years. Using the PITT-ADRC deeply phenotyped banked plasma samples, we have now begun studies on 4500 unique participants who will concomitantly have information on plasma Aβ, phosphorylated tau, glial fibrillary acidic protein (GFAP), brain- derived tau (BD-tau) and neurofilament light chain (NfL). Moreover, the participants have available neuroimaging, neuropathology and genetic data that will allow the BNGC to ask critical questions related to the performance of these biomarkers and their relationships to our well-established studies on pathology and genetic risk. In this renewal, the BNGC will address questions related to the role of genetic architecture, demographics, and comorbidities on the performance of plasma biomarkers and their clinical utility in alignment with the PITT- ADRC theme “From Neighborhoods to Neurons”. The BNGC will continue to maintain a database of fluid biomarker and genetic data as well as a biorepository containing plasma and DNA samples, both of which are available broadly to the research community. We will utilize archived plasma samples to examine the analytical robustness of AT(N) plasma biomarkers, and determine cut-points against paired neuroimaging and cognitive assessment results.