%0 Journal Article
%T CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease.
%A Delvenne A
%A Gobom J
%A Schindler SE
%A Kate MT
%A Reus LM
%A Dobricic V
%A Tijms BM
%A Benzinger TLS
%A Cruchaga C
%A Teunissen CE
%A Ramakers I
%A Martinez-Lage P
%A Tainta M
%A Vandenberghe R
%A Schaeverbeke J
%A Engelborghs S
%A Roeck E
%A Popp J
%A Peyratout G
%A Tsolaki M
%A Freund-Levi Y
%A Lovestone S
%A Streffer J
%A Barkhof F
%A Bertram L
%A Blennow K
%A Zetterberg H
%A Visser PJ
%A Vos SJB
%J Alzheimers Dement
%V 0
%N 0
%D 2024 Jul 6
%M 38970402
%F 16.655
%R 10.1002/alz.14103
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.<BR><B>CONCLUSIONS: </B>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.