{Reference Type}: Journal Article
{Title}: CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease.
{Author}: 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 E;Popp J;Peyratout G;Tsolaki M;Freund-Levi Y;Lovestone S;Streffer J;Barkhof F;Bertram L;Blennow K;Zetterberg H;Visser PJ;Vos SJB;
{Journal}: Alzheimers Dement
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 6
{Factor}: 16.655
{DOI}: 10.1002/alz.14103
{Abstract}: <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.