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.
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