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.
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This post is Copyright: 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 Tsolaki,
Yvonne Freund‐Levi,
Simon Lovestone,
Johannes Streffer,
Frederik Barkhof,
Lars Bertram,
Kaj Blennow,
Henrik Zetterberg,
Pieter Jelle Visser,
Stephanie J. B. Vos | July 6, 2024