Abstract
Introduction: Alzheimer's disease (AD) study participants may present with cognitive impairment who do not have brain amyloid deposits (Aβ-). Identifying predictive biomarkers for non-amyloid-related CI may provide better screening tests for trials seeking only CI Aβ+ participants and new therapy targets. Methods: Analysis of the Bio-Hermes biomarker database identified subpopulations of clinically normal, CN Aβ- (n = 313), CI Aβ- (n = 296), and CI Aβ+ (n = 258), and CN Aβ+ (n = 84) participants. Comparative analysis of demographics, clinical assessments, biomarkers, cytokines, and proteomics results was conducted. Results: Subgroup comparison of CI Aβ- versus CN Aβ- found that neurofilament light most clearly differentiated CI Aβ- from CN Aβ- participants. No other biomarker analysis reached a level of differential significance. Discussion: Analyses showed many novel biomarkers do not differentiate CI Aβ- from CN Aβ-. New biomarkers are needed to best determine the neuropathology of the clinical presentation of AD. Highlights: NfL differentiated CN Aβ- versus cognitively impaired Aβ-. Proteomics (two platforms) did not differentially assess cognitively impaired Aβ--. Many novel biomarkers did not differentially assess cognitively impaired Aβ-. New biomarkers are needed to determine the neuropathology of AD clinical presentation.