Biomarkers in patients with clinical signs of mild cognitive impairment or mild Alzheimer's disease but without amyloid deposits on positron emission tomography: Results from Bio‐Hermes Study participants

TL;DR

This study investigates biomarkers in patients with mild cognitive impairment or Alzheimer's disease who lack amyloid deposits, finding that neurofilament light is a key differentiator.

Contribution

The study identifies neurofilament light as a novel biomarker distinguishing amyloid-negative impaired individuals from controls.

Findings

Neurofilament light (NfL) effectively differentiates cognitively impaired amyloid-negative individuals from cognitively normal amyloid-negative individuals.

Proteomics and other novel biomarkers did not show significant differentiation between cognitively impaired and normal amyloid-negative groups.

New biomarkers are needed to better understand the neuropathology of Alzheimer's clinical presentations without amyloid deposits.

Abstract

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.

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.

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.

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.

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.

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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