Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

Antonell, Anna; Tort‐Merino, Adrià; Ríos, José; Balasa, Mircea; Borrego‐Écija, Sergi; Augé, Josep M.; Muñoz-García, Cristina; Bosch, Beatríz; Falgàs, Neus; Rami, Lorena; Ramos‐Campoy, Oscar; Blennow, Kaj; Zetterberg, Henrik; Molinuevo, José Luís; Lladó, Albert; Sánchez‐Valle, Raquel

doi:10.1016/j.jalz.2019.09.001

Cited by 56 publications

(58 citation statements)

References 45 publications

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“…They have also been genetically linked to both neurodegenerative diseases (PD, AD, and CJD) and neuropsychiatric disorders (schizophrenia and bipolar disorder). 268,269 A recent study by Antonell et al 270 found significantly increased gamma 14-3-3 concentrations in both FTD and AD compared with controls. For AD, increased concentrations were found already in a prodromal stage and the protein level was also significantly higher at later stages compared with FTD.…”

Section: Miscellaneous: Other Emerging Synaptic Biomarkersmentioning

confidence: 96%

Fluid Biomarkers for Synaptic Dysfunction and Loss

et al. 2020

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Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer’s disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.

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Section: Miscellaneous: Other Emerging Synaptic Biomarkersmentioning

confidence: 96%

Fluid Biomarkers for Synaptic Dysfunction and Loss

et al. 2020

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“…However, the authors did not consider CSF Ng as a specific marker of synaptic degeneration but rather a marker of neuronal damage ( Blennow et al, 2019 ). A recent study had a unicentric cohort of 353 participants, including HC subjects, AD, frontotemporal dementia (FTD), and CJD ( Antonell et al, 2020 ). They analyzed and compared the diagnostic accuracy and differentiating capacity of four noncore biomarkers, which stand for the distinct aspects of the neurodegeneration process ( Antonell et al, 2020 ).…”

Section: Associations Between Neurogranin and Neurological And Mentalmentioning

confidence: 99%

“…A recent study had a unicentric cohort of 353 participants, including HC subjects, AD, frontotemporal dementia (FTD), and CJD ( Antonell et al, 2020 ). They analyzed and compared the diagnostic accuracy and differentiating capacity of four noncore biomarkers, which stand for the distinct aspects of the neurodegeneration process ( Antonell et al, 2020 ). The rank of CSF Ng concentrations from lower to higher is FTD < HC < AD < CJD, which is in concordance with previously published data.…”

Section: Associations Between Neurogranin and Neurological And Mentalmentioning

confidence: 99%

“…The rank of CSF Ng concentrations from lower to higher is FTD < HC < AD < CJD, which is in concordance with previously published data. Comparing their capacity in differentiating among neurodegenerative dementias, CSF Ng shows the significant differences across all three groups (AD, FTD, and CJD) ( Antonell et al, 2020 ).…”

Section: Associations Between Neurogranin and Neurological And Mentalmentioning

confidence: 99%

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Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Xiang

Xin

Yang³

2020

Front. Aging Neurosci.

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Neurogranin (Ng) is a small protein usually expressed in granule-like structures in pyramidal cells of the hippocampus and cortex. However, its clinical value is not fully clear so far. Currently, Ng is proved to be involved in synaptic plasticity, synaptic regeneration, and long-term potentiation mediated by the calcium- and calmodulin-signaling pathways. Due to both the synaptic integrity and function as the growing concerns in the pathogenesis of a wide variety of neurological and mental diseases, a series of researches published focused on the associations between Ng and these kinds of diseases in the past decade. Therefore, in this review, we highlight several diseases, which include, but are not limited to, Alzheimer’s disease, Parkinson disease, Creutzfeldt–Jakob disease, neuro-HIV, neurosyphilis, schizophrenia, depression, traumatic brain injury, and acute ischemic stroke, and summarize the associations between cerebrospinal fluid or blood-derived Ng with these diseases. We propose that Ng is a potential and promising biomarker to improve the diagnosis, prognosis, and severity evaluation of these diseases in the future.

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“…At present, there is no cure for AD, only ve prescription drugs were approved to intend for symptom management, with varying degrees of e cacy [2]. With the deepening of studies, some theories, such as amyloid β (Aβ) deposition, tau protein abnormality, axonal transport defect, in ammatory response, and cholinergic damage, etc, have been gradually recognized [3][4][5]. The clinical and genetic trials of more-effective Alzheimer's drugs targeting anti-amyloid, anti-neuroin ammation, anti-tau, or neuroprotection are ongoing.…”

Section: Introductionmentioning

confidence: 99%

CSF FAM3C- a possible biomarker of Alzheimer’s disease

Bian

Wang

et al. 2020

Preprint

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Backgrounnd: The impact of Alzheimer's disease (AD) on the living quality and life expectancy has becoming increasingly severe, but the pathogenesis of AD is still being studied .This study aimed to investigate whether Family with sequence similarity 3 member C (FAM3C), which has been reported to be possibly associated with cognitive function, was associated with the incidence of AD.Methods: A total of 282 participants from Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included. The demographic data, cerebrospinal fluid (CSF) FAM3C content, neuropsychological scores, CSF amyloid protein level, CSF tau protein level, and imaged data were collected. One-way analysis of variance and chi-square test were used to compare demographic data, neuropsychological test scores, CSF protein levels, and imaging data of three groups. Partial correlation analysis and multiple linear regression analysis were used to investigate the relationship between FAM3C and AD diagnostic indicators in different dimensions. An ordered multi-classification logistic regression model was established to determine whether FAM3C is related to the onset of AD. Results: Lower levels of FAM3C were observed in AD and mild cognitive impairment (MCI) groups. CSF FAM3C level was related to whole-brain atrophy and temporal lobe atrophy, worse cognitive performance, decreased amyloid β 1-42 (Aβ1-42), and lower regional cerebral glucose metabolism. Conclusion: CSF FAM3C might be a potential diagnostic biomarker of AD. Further study on concrete mechanisms may contribute to early diagnosis and treatment of AD.

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Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

Cited by 56 publications

References 45 publications

Fluid Biomarkers for Synaptic Dysfunction and Loss

Fluid Biomarkers for Synaptic Dysfunction and Loss

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

CSF FAM3C- a possible biomarker of Alzheimer’s disease

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