A Blood Biomarker-guided Precision Medicine Approach for Individualized Neurodegenerative Disease Risk Reduction and Treatment: The Future of Preventive Neurology?
Kellyann Niotis1, Christopher Janney1, Shannon Helfman1, Hollie Hristov1, Nicholas Clute-Reinig1, Danny Angerbauer2, Corey Saperia3, Sara Murray1, John Westine1, Alon Seifan4, Juan Melendez-Herencia5, Praveen Parthasarathy6, Helena Colvee7, Beth Lewis1, Jessica Lakis1, Philip Sisser8, Jannatul Dishary1, Maia Mosse9, Diana Saville9, Audree Rumberger9, Michael McCullough9, Richard Isaacson1
1The Institute for Neurodegenerative Diseases (IND) Florida, 2The Atria Institute, 3Stanford University School of Medicine, 4Cognitive Neurology Consultants, Inc. dba the Neuro Well, 5Jersey Memory Assessment Service, 6Renaissance School of Medicine at Stony Brook University, 7University of Miami School of Nursing and Health Studies, 8Florida Atlantic University School of Medicine, 9BrainMind
Objective:
Explore the utility of blood-based biomarkers as outcome measures for n-of-1 neurodegenerative disease (NDD) early intervention trials.
Background:
Alzheimer's disease (AD) and other NDDs evolve over a long preclinical period, often driven by shared pathophysiological processes and modifiable risk factors. Plasma proteins (e.g., Amyloid-Beta [Aβ] and Tau isoforms) may facilitate preclinical disease detection, targeted intervention, monitoring of disease progression, and assessment of the effectiveness of personalized interventions.
Design/Methods:
The Biorepository for Alzheimer’s and Neurodegenerative Diseases Study (BioRAND) recruits subjects with family history of NDD with no/minimal neurological symptoms, and healthy controls. Subjects are referred by preventive neurology, preventive medicine, and primary care clinicians who provide individualized NDD risk reduction and/or early treatment care across the United States. Demographics, medical history, ApoE genotype, cognitive assessments, clinical and research biomarkers via venipuncture and blood spot cards are collected at baseline and longitudinally. Biomarkers include C2N LC-MS/MS Aβ42/40 ratio, Quanterix AlzPath SIMOA pTau217 assay and SIMOA Aβ, neurofilament light chain and glial fibrillary acidic protein assays, and Argo NULISA 125 biomarker CNS Panel (ANCP). Participants can opt-in to share clinical data on their treatment of modifiable NDD risk factors, including lifestyle modifications and prescribed medications (e.g., glucagon-like peptide-1 agonists, statins, anti-amyloid immunotherapies, hormone replacement therapy).
Results:
15 subjects who were provided preventive neurology care and shared clinical data (mean age, 60.2 [SD=10.63], 66.7% male, 86.7% ApoE-ε4+) were compared to 27 healthy controls at baseline. Significant differences in 42 (33.6%) of ANCP biomarkers were found. Risk reduction/early treatment subjects also showed significant changes from pre- to post-intervention in C2N Aβ42/40 (p=0.0130), ALZPath pTau217 (p=0.0063) and 26 (20.8%) ANCP biomarkers.
Conclusions:
Individualized multi-modal interventions may impact NDD blood-based biomarkers and enable clinicians to evaluate the effectiveness of preventive neurology care.
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