Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer's disease
Open accessAbstract
Introduction: Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed. Method: Solid‐phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross‐sectional studies including AD (n = 52) and controls (n = 37). Results: Increased concentrations of beta‐synuclein, gamma‐synuclein, neurogranin, phosphatidylethanolamine‐binding protein 1, and 14‐3‐3 proteins were observed in AD patients compared to controls, while neuronal pentraxin‐2 and neuronal pentraxin receptor were decreased. Discussion: We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.
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NPTXs were found to be the only markers that correlate with Aβ42 in AD.
“Accordingly, NPTXs were found to be the only markers that correlate with Aβ42 in AD (Nilsson et al. 2021).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
CSF NPTX2 levels assessed by Western Blot, in-house ELISA and mass spectrometry were decreased in both sporadic and genetic forms of MCI and AD dementia in comparison with cognitive healthy controls.
“CSF NPTX2 levels assessed by WB, in-house ELISA and mass spectrometry were decreased in both sporadic and genetic forms of MCI and AD dementia in comparison with cognitive healthy controls (Belbin et al. 2020; Galasko et al. 2019; Nilsson et al. 2021; Soldan et al. 2019; Xiao et al. 2017).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
NPTX2 weakly correlates with Aβ42, mainly in MCI.
“Some authors described a weak correlation with Aβ42, mainly in MCI (Galasko et al. 2019; Nilsson et al. 2021)”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
NPTXs moderately correlate with many synaptic markers (e.g., β-synuclein, γ-synuclein, neurogranin, syntaxin, SNAP25) in the healthy control and AD group.
“NPTXs seemed to moderately correlate with many synaptic markers (e.g., β-synuclein, γ-synuclein, neurogranin, syntaxin, SNAP25) in the healthy control and the AD group.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
CSF levels of different NPTXs strongly correlate with each other in both AD and genetic FTLD.
“Finally, CSF levels of the different NPTXs strongly correlated with each other in both AD and genetic FTLD, indicating an overall reduction of these proteins in CSF (Nilsson et al. 2021; van der Ende et al. 2020; Xiao et al. 2017).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
NPTXs might be a good candidate biomarker for disease staging and cognitive prognosis.
“Thus, they might be a good candidate biomarker for disease staging and cognitive prognosis (Galasko et al. 2019; Libiger et al. 2021; Nilsson et al. 2021; Swanson et al. 2016; Xiao et al. 2017).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
CSF NPTX levels correlate with cognitive scores in AD patients, even in the absence of brain pathology.
“Unlike core biomarkers such as Aβ (Williams et al. 2011), CSF NPTXs levels correlated with cognitive scores in AD patients, even in the absence of brain pathology.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nilsson et al. 2021
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- Authors
- Nilsson, J., Gobom, J., Sjödin, S., Brinkmalm, G., Ashton, N. J., Svensson, J., Johansson, P., Portelius, E., Zetterberg, H., Blennow, K., & Brinkmalm, A.
- Affiliations
- University of Gothenburg (SE)
- Sahlgrenska University Hospital (SE)
- King's College London (GB)
- Lund University (SE)
- Corresponding author
- Nilsson, Johanna
- ORCID
- Venue
- Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
- Publisher
- Wiley
- Published
- 2021-01
- Volume
- 13
- Issue
- 1
- Pages
- e12179-e12179
- ISSN
- 2352-8729 (ISSN-L)
- PMC
- PMC8087978
- OpenAlex
- W3162244350
- Cited by
- 82
- References
- 45
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 19 · 2023: 13 · 2022: 27 · 2021: 3
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Alzheimer's Association (ADSF-21-831377-C, ADSF‐21‐831376‐C, #ADSF-21-831381-C, ADSF-21-831376-C, #ADSF-21-831381, -21- 831377-C)
- Alzheimer's Drug Discovery Foundation (2016862, FO2017-0243, 201809, ADSF-21-831381-C, 2017-00915, #ALFGBG-715986, 201809–2016862, ADSF-21-831377-C, 860197, JPND2019-466-236, 201809-2016615, #ADSF-21-831376-C, #RDAPB‐201809‐2016615, AF-742881)
- Familjen Erling-Perssons Stiftelse (FO2019-0228, 860197)
- EU Joint Programme – Neurodegenerative Disease Research (JPND2019-466-236)
- European Commission (HORIZON2020, JPND2019‐466‐236, 860197)
- Hjärnfonden (FO2017‑0243, FO2017, ALFGBG-715986, FO2019‐0228, JPND2019-466-236)
- Vetenskapsrådet (2017-00915, (#ALFGBG-715986, 681712, 2018-, JPND2019-466-236, FO2017-0243, 2018-02532)
- Alzheimerfonden (AF-742881, AF-930934)
- UK Dementia Research Institute (#2017-00915)
- Demensfonden
- Olav Thon Stiftelsen (#FO2019-0228)
- H2020 European Research Council (681712)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, synaptic dysfunction, synaptic proteins, beta-synuclein, gamma-synuclein, neurogranin, 14-3-3 proteins, NPTX2, biomarker panel
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