Establishing an Alzheimer’s disease biomarker clock in Down syndrome using positron emission tomography and plasma analytes
NIH/NIA RF1AG094739
Contact PI: Matthew Zammit
M-PI: Tobey Betthauser
09/15/2025-08/31/2029
Alzheimer’s disease has emerged as the leading cause of death for adults with Down syndrome over the age of 35, yet the timeline of disease progression remains understudied. This project aims to address this public health need by characterizing AD biomarker progression in the DS population at various stages of the disease, allowing for better insight into the initiation of AD treatment based on biomarker level and disease stage. To pinpoint suitable treatment windows at varying stages of DSAD, this project will model AD biomarker progression through the novel Biomarker Clock Framework, which creates a timeline of disease progression based on the onset of abnormal biomarker presence.
Multicohort study of factors that influence AD biomarker and dementia timing
NIH/NIA R01AG080766
PI: Tobey Betthauser
02/01/2023-11/30/2027
This study aims to identify common factors across existing data from the Washington University Knight ADRC, the Wisconsin Alzheimer’s Disease Research Center, the Wisconsin Registry for Alzheimer’s Prevention, the Mayo Clinic Study of Aging, and the Alzheimer’s Disease Neuroimaging Initiative that influence the timing of events in Alzheimer’s disease. Variables of interest include, the onset of beta-amyloid pathology, onset of tau pathology, neurodegeneration, and the time between pathology onset and clinical symptoms. This study will also investigate the possible role of social determinant of health including neighborhood disadvantage in affecting the timing of these events across multiple cohorts.
Postmortem Validation of Tau PET Ligand [18F]MK6240

UW-Madison OVCRGE
PI: Tobey Betthauser
06/2021 – Ongoing
In collaboration with Dr. Milos Ikonomovic at the University of Pittsburgh, this study compares antemortem tau positron emission tomography (PET) imaging with [18F]MK-6240 with postmortem validation and quantification of tau, amyloid, and other brain pathologies to understand the molecular signature of [18F]MK-6240 that drives in vivo tau PET imaging.
Postmortem Validation of 4D Flow MRI for Neuroimaging
UW-Madison OVCRGE
PI: Tobey Betthauser
04/2021 – 10/2024
4D Flow magnetic resonance imaging (MRI) is a method developed to characterize the properties of larger vessels during life. This study compares antemortem 4D Flow imaging with postmortem characterization of cerebral vessels to understand the correspondence between vessel pathology and vessel health, and antemortem 4D flow MRI outcomes.
PUBLICATIONS:
Cerebral artery and brain pathology correlates of antemortem cerebral artery 4D flow MRI
Imaging Neuroscience (2024)
First Author: Brooke E. Schroeder
