Journal Article

CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease

Streffer, Johannes, Engelborghs, Sebastiaan, Vos, Stephanie J. B., Peyratout, Gwendoline, Tijms, Betty M., Freund‐Levi, Yvonne, Teunissen, Charlotte E., Cruchaga, Carlos, Dobricic, Valerija, Kate, Mara ten, Schindler, Suzanne E., Tsolaki, Magda, Barkhof, Frederik, Schaeverbeke, Jolien, Zetterberg, Henrik, Bertram, Lars, Benzinger, Tammie L. S., Roeck, Ellen De, Gobom, Johan, Visser, Pieter Jelle, Reus, Lianne M., Martinez‐Lage, Pablo, Ramakers, Inez, Blennow, Kaj, Delvenne, Aurore, Tainta, Mikel, Vandenberghe, Rik, Popp, Julius, Lovestone, Simon

2024

Overview

INTRODUCTION We aimed to unravel the underlying pathophysiology of the neurodegeneration (N) markers neurogranin (Ng), neurofilament light (NfL), and hippocampal volume (HCV), in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics. METHODS Individuals without dementia were classified as A+ (CSF amyloid beta [Aβ]42), T+ (CSF phosphorylated tau181), and N+ or N− based on Ng, NfL, or HCV separately. CSF proteomics were generated and compared between groups using analysis of covariance. RESULTS Only a few individuals were A+T+Ng−. A+T+Ng+ and A+T+NfL+ showed different proteomic profiles compared to A+T+Ng− and A+T+NfL−, respectively. Both Ng+ and NfL+ were associated with neuroplasticity, though in opposite directions. Compared to A+T+HCV−, A+T+HCV+ showed few proteomic changes, associated with oxidative stress. DISCUSSION Different N markers are associated with distinct neurodegenerative processes and should not be equated. N markers may differentially complement disease staging beyond amyloid and tau. Our findings suggest that Ng may not be an optimal N marker, given its low incongruency with tau pathophysiology. Highlights In Alzheimer's disease, neurogranin (Ng)+, neurofilament light (NfL)+, and hippocampal volume (HCV)+ showed differential protein expression in cerebrospinal fluid. Ng+ and NfL+ were associated with neuroplasticity, although in opposite directions. HCV+ showed few proteomic changes, related to oxidative stress. Neurodegeneration (N) markers may differentially refine disease staging beyond amyloid and tau. Ng might not be an optimal N marker, as it relates more closely to tau.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aged / Alzheimer Disease - cerebrospinal fluid / Alzheimer Disease - pathology / Alzheimer's disease / Amyloid beta-Peptides - cerebrospinal fluid / Analysis of covariance / Atrophy / Biological markers / Biomarkers / Biomarkers - cerebrospinal fluid / Brain research / Cerebrospinal fluid / Clinical trials / Dementia / Disease / Enzymes / Female / Genomes / Hepatitis C / hippocampal volume / Hippocampus - pathology / Humans / Immunoassay / Magnetic resonance imaging / Male / Memory / Middle Aged / Mild cognitive impairment / Neurochemistry / Neurodegeneration / neurodegeneration markers / neurofilament light / Neurofilament Proteins - cerebrospinal fluid / neurogranin / Neurogranin - cerebrospinal fluid / Neuropsychology / Oxidative stress / Pathophysiology / Peptide Fragments - cerebrospinal fluid / Peptides / Plasticity / Proteins / Proteomics / Stress / tau Proteins - cerebrospinal fluid