TY - JOUR
T1 - CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease
AU - Delvenne, Aurore
AU - Gobom, Johan
AU - Schindler, Suzanne E.
AU - Kate, Mara ten
AU - Reus, Lianne M.
AU - Dobricic, Valerija
AU - Tijms, Betty M.
AU - Benzinger, Tammie L.S.
AU - Cruchaga, Carlos
AU - Teunissen, Charlotte E.
AU - Ramakers, Inez
AU - Martinez-Lage, Pablo
AU - Tainta, Mikel
AU - Vandenberghe, Rik
AU - Schaeverbeke, Jolien
AU - Engelborghs, Sebastiaan
AU - Roeck, Ellen De
AU - Popp, Julius
AU - Peyratout, Gwendoline
AU - Tsolaki, Magda
AU - Freund-Levi, Yvonne
AU - Lovestone, Simon
AU - Streffer, Johannes
AU - Barkhof, Frederik
AU - Bertram, Lars
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Visser, Pieter Jelle
AU - Vos, Stephanie J.B.
N1 - Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - biomarkers
KW - cerebrospinal fluid
KW - hippocampal volume
KW - neurodegeneration markers
KW - neurofilament light
KW - neurogranin
KW - pathophysiology
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=85197672291&partnerID=8YFLogxK
U2 - 10.1002/alz.14103
DO - 10.1002/alz.14103
M3 - Article
C2 - 38970402
AN - SCOPUS:85197672291
SN - 1552-5260
VL - 20
SP - 6205
EP - 6220
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 9
ER -