Alzheimer Award

2024 Awardee

Robert A. Rissman, PhD

Read the press release here

Robert A. Rissman, PhD, received his Doctorate in Neuroscience from Drexel University School of Medicine in Philadelphia, PA. He is the W.M. Keck Endowed Chair in Medicine and Professor of Physiology and Neuroscience at the University of Southern California (USC). He is Founding Director of the Neuroscience Translational Research Division at USC’s Alzheimer’s Therapeutic Research Institute in San Diego, CA. His research is predominantly focused on validating plasma biomarkers for Alzheimer’s disease and related dementias (ADRD) that can be used to understand disease etiology and as screening tools for clinical trials. His work is also centered on developing and testing novel therapeutics or ADRD in animal and in vitro models, particularly from the perspective of informing on and predicting comorbidity. In addition to his basic science translational research, Dr. Rissman is a member of the NACC Biomarker Steering Committee and the Biomarker lead for the Alzheimer’s Clinical Trials Consortium (ACTC) and the USC Alzheimer’s Disease Research Center (ADRC). He has published more than 200 peer-reviewed articles.

Importance of Published Article
“Evaluation of Blood-Based Plasma Biomarkers as Potential Markers of Amyloid Burden in Preclinical Alzheimer’s Disease.”

The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) was a groundbreaking, first of its kind secondary prevention phase 3 trial that sought to test the impact of Solanezumab-mediated lowering of monomeric amyloid in 1169 asymptomatic individuals at risk for progression to AD. Eligibility was determined by amyloid PET and participants were determined to be amyloid elevated/positive or non-elevated/negative. Although safe over the time treatment and having a modest, but significant effect on amyloid PET, Solaneuzumab was not found to be efficacious on its primary endpoint, mean change in the Preclinical Alzheimer Cognitive Composite (PACC) score. Despite the trial being negative, the data and biomarker resources that came from the trial are invaluable for future research. For example, given the variety of issues surrounding use of amyloid PET or CSF as screening tools for identifying amyloid positive participants, we assessed how newly developed blood-based biomarkers performed for predicting amyloid PET results in A4. In our study we used biobanked plasma from the screening visits of the A4 study to determine whether plasma Aβ40, Aβ42, and Aβ42/Aβ40 levels, as measured by two different IP-MS platforms (MALDI-TOF-MS and LC-MS/MS), can predict brain amyloid PET positivity, A4 study participants. We also determined the impact of two different plasma processing protocols (2 h vs. 24 h) on plasma Aβ40, Aβ42, and Aβ42/Aβ40 levels to predict amyloid PET positivity. Recently published data suggest that lower plasma Aβ42/Aβ40 ratios, as measured using IP-MS, are associated with brain amyloid pathology, accelerated cognitive decline, and increased risk of developing AD dementia. In our study, we found that plasma Aβ42/Aβ40 quantified using either of the available MS method can predict screening amyloid PET positivity in the A4 trial. We also found that blood samples that were collected and processed to plasma within 2 h after blood draw had increased utility for prediction of amyloid PET status compared to blood samples that were shipped overnight on cold packs and processed to plasma within 24 h after blood draw. Overall, our findings demonstrate that plasma screening testing using Aβ42/Aβ40 can be used to identify eligible, cognitively normal individuals for AD prevention trials. Using plasma screening analyses for enrollment in prevention trials can reduce traditional screen-failure rates and save time, funds and burden on sites and participants.