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Increased CSF neurogranin concentration is specific to Alzheimer disease
Open accessAbstract
OBJECTIVE: To assess the specificity of the dendritic protein neurogranin (Ng) in CSF from patients with a broad range of neurodegenerative diseases including a variety of dementias, tauopathies, and synucleinopathies. METHOD: An optimized immunoassay was used to analyze CSF Ng in a retrospective cohort of 331 participants with different neurodegenerative diseases, including healthy controls (n = 19), biomarker-proven Alzheimer disease (AD) (n = 100), genetic AD (n = 2), behavioral variant frontotemporal dementia (n = 20), speech variant frontotemporal dementia (n = 21), Lewy body dementia (n = 13), Parkinson disease (n = 31), progressive supranuclear palsy (n = 46), multiple system atrophy (n = 29), as well as a heterogeneous group with non-neurodegenerative cognitive impairment (n = 50). CSF Ng concentrations and correlations of CSF Ng with total tau, phosphorylated tau, and β-amyloid 42 concentrations, Mini-Mental State Examination score, and disease duration in the different groups were investigated. RESULTS: Median CSF Ng concentration was higher in patients with AD compared to both controls (p < 0.001) and all other disease groups (all p < 0.001) except speech variant frontotemporal dementia. There were no significant differences in CSF Ng concentrations between any other neurodegenerative groups and controls. In addition, we found strong correlations between Ng and total tau (p < 0.001) and phosphorylated tau (p < 0.001). CONCLUSIONS: These results confirm an increase in CSF Ng concentration in patients with AD as previously reported and show that this is specific to AD and not seen in a range of other neurodegenerative diseases.
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“Similar results have been reported in a previous cohort consisting of AD and FTD patients [30].”
In the citing paper
“Another hypothesis is that the increased CSF synaptic protein concentration may be a consequence of the protein leakage into the interstitial fluid upon synaptic damage and early neuronal loss (Wellington et al. 2016);”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Wellington et al. 2016
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“the CSF neurogranin increases exclusively in AD patients and has not been observed in other neurodegenerative disorders, such as frontotemporal dementia or Parkinson’s disease.550”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [550]
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“More importantly, the CSF neurogranin increases exclusively in AD patients and has not been observed in other neurodegenerative disorders, such as frontotemporal dementia or Parkinson’s disease.(550) MicroRNA (miRNA) are noncoding RNA molecules of 20–25 nucleotides that can manipulate gene expression posttranscription…”
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Metadata
- Authors
- Wellington, H., Paterson, R. W., Portelius, E., Törnqvist, U., Magdalinou, N., Fox, N. C., Blennow, K., Schott, J. M., & Zetterberg, H.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- Venue
- Neurology
- Published
- 2016-03
- Volume
- 86
- Issue
- 9
- Pages
- 829-835
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4793782
- OpenAlex
- W2289040490
- Cited by
- 232
- References
- 42
- Citations by year
- 2026: 3 · 2025: 17 · 2024: 31 · 2023: 15 · 2022: 27 · 2021: 38 · 2020: 30 · 2019: 24 · 2018: 24 · 2017: 15 · 2016: 7
- FWCI
- 20.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Torsten Söderbergs Stiftelse
- National Institute for Health and Care Research (NF-SI-0513-10134, NF-SI-0508-10123)
- European Commission (666992, H2020, H2020-PHC-2014, H2020-PHC)
- Wolfson Foundation
- Hjärnfonden
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Alzheimerfonden
- University College London Hospitals NHS Foundation Trust
- California State University, Bakersfield
- Horizon 2020 Framework Programme (666992, -2014-2015, H2020-PHC-2014)
- Medical Research Council (CSUB19166)
- Engineering and Physical Sciences Research Council (EP/J020990/1, H2020, J020990)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- neurogranin, cerebrospinal fluid biomarkers, Alzheimer's disease, dementia, frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease, progressive supranuclear palsy, multiple system atrophy, tau protein, phosphorylated tau, amyloid-beta 42, diagnostic specificity
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, London, Male, Middle Aged, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Up-Regulation, Prevalence, Risk Assessment, Neurogranin
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