Robert A. Rissman, Ph.D., receives the 2024 Alzheimer Award

This annual award recognizes outstanding contributions to the advancement of AD research published in the Journal of Alzheimer’s Disease

Amsterdam, 9 July 2024 – The Journal of Alzheimer’s Disease (JAD) is pleased to announce that Robert A. Rissman, PhD, University of Southern California, is the recipient of the 2024 Alzheimer Award. He is lead author of the groundbreaking article “Evaluation of Blood-Based Plasma Biomarkers as Potential Markers of Amyloid Burden in Preclinical Alzheimer’s Disease.” The award is proudly sponsored by JAD’s publisher IOS Press, now part of Sage.

In the 2024 award-winning paper Dr. Rissman and his co-investigators present important insights into the potential and accuracy of using a blood test to screen for amyloid in the brain. The presence of amyloid plaques is characteristic of Alzheimer’s disease (AD) and related dementias. The article is freely available to everyone to read, download, and share.

“Current AD diagnostics are expensive, not readily accessible in primary care settings, time consuming, and invasive,” explains Dr. Rissman. “These limitations have sparked researchers to examine the feasibility of using blood biomarker measures to detect amyloid pathology. Blood sample collection is procedurally simple and readily accessible in primary care settings to minority populations in rural areas, the elderly, and those of diverse socioeconomic groups. Moreover, blood-based biomarkers may serve as a more cost-effective screening tool for patient enrollment into preclinical AD trials.”

The study used biobanked plasma from the screening visits of participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4), a first-of-its-kind secondary prevention phase 3 trial that sought to test the impact of solanezumab-mediated lowering of monomeric amyloid on cognition: The trial included 1169 asymptomatic individuals at risk for progression to AD. Eligibility was determined by amyloid positron emission tomography (PET), and participants were included if found to be amyloid elevated/positive. Although safe over the treatment time and having a 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 outcome being negative, the data and biomarker resources that came from the trial are invaluable for future research,” notes Dr. Rissman. “For example, given the variety of issues surrounding use of amyloid PET or cerebrospinal fluid as screening tools for identifying amyloid positive participants, we assessed how newly developed blood-based biomarkers performed for predicting amyloid PET results in A4.”

The biobanked plasma was used to determine whether plasma Aβ40, Aβ42, and Aβ42/Aβ40 levels, as measured by two different immunoprecipitation mass spectrometry (IP-MS) platforms (MALDI-TOF-MS and LC-MS/MS), could predict brain amyloid PET positivity. Investigators also determined the impact of two different plasma processing protocols (2 hours vs. 24 hours) on plasma Aβ40, Aβ42, and Aβ42/Aβ40 levels for predicting amyloid PET positivity.

Recently published data suggest that 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.

The study found that plasma Aβ42/Aβ40 ratio quantified using either of the available MS methods can predict screening amyloid PET positivity in the A4 trial. It also determined that blood samples collected and processed to plasma within 2 hours 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 24 hours after blood draw.

According to Dr. Rissman, “Overall, our findings demonstrate that Aβ42/Aβ40 plasma testing in AD prevention trials screening can be used to identify amyloid PET positive, cognitively normal individuals. 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.”

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.

“The editorial board and I are delighted to present Dr. Rissman with the Alzheimer Award for his outstanding work reported in the award-winning study, as well as for his career of excellence. Blood-based biomarkers are a major advance over more invasive CSF or PET analyses but require careful validation. In coupling his studies with the A4 trials Dr. Rissman demonstrated blood biomarkers can be validated by parallel PET analysis,” comments George Perry, PhD, Semmes Foundation Distinguished University Chair in Neurobiology, The University of Texas at San Antonio, and Editor-in-Chief of JAD.

Each year, members of JAD’s extensive editorial board select the article published during the previous year that has had the most significant impact on AD research. The awardee receives the Alzheimer Medal, a bronze medal featuring the likeness of Alois Alzheimer, and a monetary award of $7,500. The award will be formally presented at the JAD Editorial Board meeting in Philadelphia on July 29, 2024, in conjunction with the Alzheimer's Association International Conference.