Explore the utility of blood-based biomarkers as outcome measures for n-of-1 neurodegenerative disease (NDD) early intervention trials.

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).

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.