| Title: |
CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| Authors: |
Delvenne, A; Gobom, J; Schindler, SE; Kate, MT; Reus, LM; Dobricic, V; Tijms, BM; Benzinger, TLS; Cruchaga, C; Teunissen, CE; Ramakers, I; Martinez‐Lage, P; Tainta, M; Vandenberghe, R; Schaeverbeke, J; Engelborghs, S; Roeck, ED; Popp, J; Peyratout, G; Tsolaki, M; Freund‐Levi, Y; Lovestone, S; Streffer, J; Barkhof, F |
| Publisher Information: |
Wiley Open Access |
| Publication Year: |
2024 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1002/alz.14103 |
| DOI: |
10.1002/alz.14103 |
| Availability: |
https://doi.org/10.1002/alz.14103; https://ora.ox.ac.uk/objects/uuid:a95f1a7b-5133-47ea-8112-88b7d2b4b3fa |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) |
| Accession Number: |
edsbas.48AC998 |
| Database: |
BASE |