Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia
Abstract Background Loss of synaptic functionality has been recently identified as an early-stage indicator of neurological diseases. Consequently, monitoring changes in synaptic protein levels may be relevant for observing disease evolution or treatment responses in patients. Here, we have studied...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-023-01212-x |
| _version_ | 1827979618922004480 |
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| author | Shreyasee Das Julie Goossens Dirk Jacobs Nele Dewit Yolande A. L. Pijnenburg Sjors G. J. G. In ‘t Veld Charlotte E. Teunissen Eugeen Vanmechelen |
| author_facet | Shreyasee Das Julie Goossens Dirk Jacobs Nele Dewit Yolande A. L. Pijnenburg Sjors G. J. G. In ‘t Veld Charlotte E. Teunissen Eugeen Vanmechelen |
| author_sort | Shreyasee Das |
| collection | DOAJ |
| description | Abstract Background Loss of synaptic functionality has been recently identified as an early-stage indicator of neurological diseases. Consequently, monitoring changes in synaptic protein levels may be relevant for observing disease evolution or treatment responses in patients. Here, we have studied the relationship between fluid biomarkers of neurodegeneration and synaptic dysfunction in patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD), and subjective cognitive decline (SCD). Methods The exploratory cohort consisted of cerebrospinal fluid (CSF) samples (n = 60) from patients diagnosed with AD (n = 20), FTD (n = 20), and SCD (n = 20) from the Amsterdam Dementia Cohort. We developed two novel immunoassays for the synaptic proteins synaptosomal-associated protein-25 (SNAP25) and vesicle-associated membrane protein-2 (VAMP2). We measured the levels of these biomarkers in CSF, in addition to neuronal pentraxin-2 (NPTX2), glutamate ionotropic receptor-4 (GluR4), and neurogranin (Ng) for this cohort. All in-house immunoassays were validated and analytically qualified prior to clinical application. CSF neurogranin (Ng) was measured using a commercially available ELISA. Results This pilot study indicated that SNAP25, VAMP2, and Ng may not be specific biomarkers for AD as their levels were significantly elevated in patients with both AD and FTD compared to SCD. Moreover, the strength of the correlations between synaptic proteins was lower in the AD and FTD clinical groups compared to SCD. SNAP25, VAMP2, and Ng correlated strongly with each other as well as with total Tau (Tau) and phosphorylated Tau (PTau) in all three clinical groups. However, this correlation was weakened or absent with NPTX2 and GluR4. None of the synaptic proteins correlated to neurofilament light (NfL) in any clinical group. Conclusion The correlation of the synaptic biomarkers with CSF Tau and PTau but the lack thereof with NfL implies that distinct pathological pathways may be involved in synaptic versus axonal degeneration. Our results reflect the diversity of synaptic pathology in neurodegenerative dementias. |
| first_indexed | 2024-04-09T21:39:33Z |
| format | Article |
| id | doaj.art-ec43194304df4597904742a63243c439 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-04-09T21:39:33Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-ec43194304df4597904742a63243c4392023-03-26T11:07:36ZengBMCAlzheimer’s Research & Therapy1758-91932023-03-0115111110.1186/s13195-023-01212-xSynaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementiaShreyasee Das0Julie Goossens1Dirk Jacobs2Nele Dewit3Yolande A. L. Pijnenburg4Sjors G. J. G. In ‘t Veld5Charlotte E. Teunissen6Eugeen Vanmechelen7ADxNeuroSciences NVADxNeuroSciences NVADxNeuroSciences NVMedpaceNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit AmsterdamNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit AmsterdamNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit AmsterdamADxNeuroSciences NVAbstract Background Loss of synaptic functionality has been recently identified as an early-stage indicator of neurological diseases. Consequently, monitoring changes in synaptic protein levels may be relevant for observing disease evolution or treatment responses in patients. Here, we have studied the relationship between fluid biomarkers of neurodegeneration and synaptic dysfunction in patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD), and subjective cognitive decline (SCD). Methods The exploratory cohort consisted of cerebrospinal fluid (CSF) samples (n = 60) from patients diagnosed with AD (n = 20), FTD (n = 20), and SCD (n = 20) from the Amsterdam Dementia Cohort. We developed two novel immunoassays for the synaptic proteins synaptosomal-associated protein-25 (SNAP25) and vesicle-associated membrane protein-2 (VAMP2). We measured the levels of these biomarkers in CSF, in addition to neuronal pentraxin-2 (NPTX2), glutamate ionotropic receptor-4 (GluR4), and neurogranin (Ng) for this cohort. All in-house immunoassays were validated and analytically qualified prior to clinical application. CSF neurogranin (Ng) was measured using a commercially available ELISA. Results This pilot study indicated that SNAP25, VAMP2, and Ng may not be specific biomarkers for AD as their levels were significantly elevated in patients with both AD and FTD compared to SCD. Moreover, the strength of the correlations between synaptic proteins was lower in the AD and FTD clinical groups compared to SCD. SNAP25, VAMP2, and Ng correlated strongly with each other as well as with total Tau (Tau) and phosphorylated Tau (PTau) in all three clinical groups. However, this correlation was weakened or absent with NPTX2 and GluR4. None of the synaptic proteins correlated to neurofilament light (NfL) in any clinical group. Conclusion The correlation of the synaptic biomarkers with CSF Tau and PTau but the lack thereof with NfL implies that distinct pathological pathways may be involved in synaptic versus axonal degeneration. Our results reflect the diversity of synaptic pathology in neurodegenerative dementias.https://doi.org/10.1186/s13195-023-01212-xBiomarkersImmunoassaySynapseDementiaAlzheimer’s diseaseFrontotemporal dementia |
| spellingShingle | Shreyasee Das Julie Goossens Dirk Jacobs Nele Dewit Yolande A. L. Pijnenburg Sjors G. J. G. In ‘t Veld Charlotte E. Teunissen Eugeen Vanmechelen Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia Alzheimer’s Research & Therapy Biomarkers Immunoassay Synapse Dementia Alzheimer’s disease Frontotemporal dementia |
| title | Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia |
| title_full | Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia |
| title_fullStr | Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia |
| title_full_unstemmed | Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia |
| title_short | Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia |
| title_sort | synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with alzheimer s disease and frontotemporal dementia |
| topic | Biomarkers Immunoassay Synapse Dementia Alzheimer’s disease Frontotemporal dementia |
| url | https://doi.org/10.1186/s13195-023-01212-x |
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