These are early detection tools never before offered to patients in the clinical setting and are part of the Davos Alzheimer’s Collaborative (DAC) Healthcare System Preparedness Project and Accurate Diagnosis Program.
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DAC is a pioneering worldwide initiative seeking to cure Alzheimer’s disease and dementia. The effort at Mount Sinai is co-led by Fanny Elahi, MD, PhD, Director of Fluid Biomarkers at the Barbara and Maurice Deane Center for Wellness and Cognitive Health and Co-Director of Biomarkers and Genetics Research for the Mount Sinai Alzheimer’s Disease Research Center, and Georges Naasan, MD, Co-Chief and Medical Director for the Division of Behavioral Neurology and Neuropsychiatry, and Co-Director of the Deane Center.
From left: Liqwha Ncube, Clinical Research Manager; Georges Naasan, MD; Fanny Elahi, MD, PhD; and Briella Smaw, Clinical Research Coordinator.
“Knowledge gained from blood-based biomarkers of Alzheimer’s and related dementias provides a unique opportunity for early disease detection and, consequently, intervention, and will enable implementation of existing treatments as well as discovery of novel therapeutics,” says Dr. Elahi, Associate Professor of Neurology, and Neuroscience, at the Icahn School of Medicine at Mount Sinai. “Our work with the DAC Accurate Diagnosis Program will not only help us stratify patients rapidly, noninvasively, and cost-effectively, but also shed light on the best practices for implementation of these revolutionary diagnostic tests in real-world clinical settings. We are excited to bring blood-based biomarkers to the clinic.”
Adds Dr. Naasan, “Clinicians have been waiting for a long time for ways to confirm the presence of Alzheimer’s disease biomarkers that do not pose risks to patients or financially strain the health system. This project is a first step in this direction and has the potential of revolutionizing clinical care for Alzheimer’s disease. Blood-based biomarkers also have the potential of becoming the tests needed to select patients for targeted therapies, including newly U.S. Food and Drug Administration-approved monoclonal antibodies, which can only be administered to those who obtain a PET scan or a spinal tap that confirms the presence of Alzheimer’s disease.”
These are early detection tools never before offered to patients in the clinical setting and are part of the Davos Alzheimer’s Collaborative (DAC) Healthcare System Preparedness Project and Accurate Diagnosis Program.
Drs. Elahi and Naasan, through a $1.3 million grant from the Davos Alzheimer’s Collaborative, will lead a team of physicians, nurses, social workers, clinical research coordinators and data scientists from Mount Sinai to recruit 900 patients over the next nine months. Patients will be recruited from the Deane Center, The Mount Sinai Hospital-based memory loss center and from the hospital’s geriatric and primary care clinics and followed for six months afterward. Mount Sinai is one of the largest academic health systems in the New York metropolitan area, with a strong history of enrolling both socioeconomically and racially/ethnically diverse patients into research studies. “This will prove incredibly helpful in informing the most effective ways to transition these blood-based biomarkers from the research world, which tends to have a high level of homogeneity, to the highly diverse real world,” Dr. Elahi says.
“Many people think of the amyloid-beta protein as the culprit associated with Alzheimer’s disease pathology; however, we now know that pathological forms of the protein tau are the more toxic substrates of disease. We are utilizing a biomarker that captures a toxic form of this protein and also predicts brain deposits of amyloid-beta. P-Tau 217 will be the primary biomarker in this study, and we will also examine levels of two more proteins (NfL and GFAP) that indicate whether the brain is degenerating,” says Dr. Elahi. “Notably, these additional proteins are not specific to any subtype of disease. Their levels go up across the spectrum of brain degenerative disorders from dementia-causing disease to multiple sclerosis, and infection- or concussion-related brain dysfunction. By quantifying three proteins in blood, we will be able to determine risk of Alzheimer’s disease as well as brain degeneration of any cause.”
The Mount Sinai team will be utilizing the LucentAD p-Tau 217 assay, a noninvasive blood test that relies on quantitation of the tau isoform that is phosphorylated at the 217 amino acid residue (p-Tau 217) in plasma. This quantification provides rule-in/rule-out data that could impact final diagnosis of Alzheimer’s disease in patients with cognitive impairment. Lucent Diagnostics, the commercial brand of Quanterix, is powered by ultra-sensitive
Simoa® technology that bridges the gap between research and clinical implementation. The Mount Sinai team selected Lucent as its industry partner because it was able to provide highly accurate tests for all three proteins.
“This project is critical for providing noninvasive, low-cost testing options and improving how we diagnose and treat these disorders,” says Dr. Elahi. “What we’re measuring today is just the tip of the iceberg, however. There are numerous additional pathologies for which my lab and others are developing novel biomarker tests. Moving detection of brain degenerative disorders to blood is an incredible leap forward toward slowing down disease progression and, ultimately, developing cures for dementia-causing pathologies.”
The p-tau 217 will be the primary biomarker in this study.
We will also examine levels of two more proteins (NfL and GFAP).
George Vradenburg is founding chairman of the Davos Alzheimer’s Collaborative. “The Mount Sinai Health System will play a critical role in the Davos Alzheimer’s Collaborative global Accurate Diagnosis Program, helping to catalyze health care system change and making patient-centered care and support more widely accessible,” he says.
The Mount Sinai team will share learnings with the Davos Alzheimer’s Collaborative Healthcare System Preparedness Project in regular community-of-practice meetings throughout the 18-month project. To benefit other health systems interested in adopting similar efforts, the learnings and practical resources from the DAC Accurate Diagnosis Program will be shared as part of the Davos Alzheimer’s Collaborative Early Detection Blueprint.
Other sites participating in the DAC Accurate Diagnosis Program include: the University of Kansas Health System and University of Kansas Alzheimer’s Disease Research Center; Wake Forest University School of Medicine; Alzheimer Center Amsterdam at Amsterdam University Medical Center; Imperial College London and Imperial College Healthcare NHS Trust; Ludwig-Maximillians-University (LMU) Hospital Munich–Alzheimer’s Therapy and Research Center; and Tokyo Metropolitan Institute for Geriatrics and Gerontology.