# 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.

## Key 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.