CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease

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

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)6205-6220
Number of pages16
JournalAlzheimer's and Dementia
Volume20
Issue number9
DOIs
StatePublished - Sep 2024

Keywords

  • Alzheimer's disease
  • biomarkers
  • cerebrospinal fluid
  • hippocampal volume
  • neurodegeneration markers
  • neurofilament light
  • neurogranin
  • pathophysiology
  • proteomics

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