CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease
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 cla...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Wiley Open Access
2024
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| _version_ | 1826313486240579584 |
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| 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, ED Popp, J Peyratout, G Tsolaki, M Freund‐Levi, Y Lovestone, S Streffer, J Barkhof, F |
| author_facet | 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 |
| author_sort | Delvenne, A |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-09-25T04:15:53Z |
| format | Journal article |
| id | oxford-uuid:a95f1a7b-5133-47ea-8112-88b7d2b4b3fa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:15:53Z |
| publishDate | 2024 |
| publisher | Wiley Open Access |
| record_format | dspace |
| spelling | oxford-uuid:a95f1a7b-5133-47ea-8112-88b7d2b4b3fa2024-07-15T20:03:49ZCSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a95f1a7b-5133-47ea-8112-88b7d2b4b3faEnglishJisc Publications RouterWiley Open Access2024Delvenne, AGobom, JSchindler, SEKate, MTReus, LMDobricic, VTijms, BMBenzinger, TLSCruchaga, CTeunissen, CERamakers, IMartinez‐Lage, PTainta, MVandenberghe, RSchaeverbeke, JEngelborghs, SRoeck, EDPopp, JPeyratout, GTsolaki, MFreund‐Levi, YLovestone, SStreffer, JBarkhof, FINTRODUCTION: 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. |
| spellingShingle | 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 CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| title | CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| title_full | CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| title_fullStr | CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| title_full_unstemmed | CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| title_short | CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease |
| title_sort | csf proteomic profiles of neurodegeneration biomarkers in alzheimer s disease |
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