Neurogranin as biomarker in CSF is non-specific to Alzheimer's disease dementia

Willemse, Eline A.J.; Sieben, Anne; Somers, Charisse; Vermeiren, Yannick; Roeck, Naomi De; Timmers, Maarten; Broeckhoven, Christine Van; Vil, Bart De; Cras, Patrick; Deyn, Peter Paul De; Martin, Jean‐Jacques; Teunissen, Charlotte E.; Engelborghs, Sebastiaan; Bjerke, Maria

doi:10.1016/j.neurobiolaging.2021.08.002

Cited by 16 publications

(10 citation statements)

References 57 publications

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“…Recently, a study contradicting the previous studies of neurogranin as a diagnostic marker reported that neurogranin fails to differentially diagnose AD. 101 The analysis of CSF synaptotagmin, another synaptic marker, by the MS-based approach showed signicantly increased levels in MCI and AD cases, which demonstrates the ability to discriminate both these clinical conditions. 102 In a longitudinal clinical study, the analysis of a soluble triggering receptor expressed on myeloid cells 2 (sTREM2, a microglial marker) changes in CSF and its association with other biomarkers demonstrates its diagnostic ability in autosomal dominant AD cases.…”

Section: Circulating Biomarkersmentioning

confidence: 89%

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

Ramesh

Govindaraju

2022

Chem. Sci.

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Section: Circulating Biomarkersmentioning

confidence: 89%

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

Ramesh

Govindaraju

2022

Chem. Sci.

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“…In a study on vascular dementia, plasma NRG1 levels were found to be increased and inversely correlated to cognitive severity [ 38 ]. Neuropathological studies and synaptic CSF biomarker results have highlighted the fact that synapse dysfunction is a prominent feature in AD but that it is not entirely specific to it [ 39 , 40 ]. It can also be observed in non-AD dementia, although to a much lesser extent than in AD, a finding in line with our results [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma neuregulin 1 as a synaptic biomarker in Alzheimer’s disease: a discovery cohort study

et al. 2022

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Background Synaptic dysfunction is an early core feature of Alzheimer’s disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest. Objective To measure plasma NRG1 concentration in AD patients in comparison with other neurodegenerative disorders and neurological controls (NC) and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers. Methods This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n = 27) and at dementia stage (n = 35), non-AD dementia (n = 26, Aβ-negative), non-AD MCI (n = 19), and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (Aβ 42/Aβ 40 ratio, phospho-tau, and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25. Results Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P = 0.005 and P < 0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (β = 0.372, P = 0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in Aβ-positive patients (β = −0.197–0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin, and SNAP-25 (β = 0.278–0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in Aβ-positive patients (all, β = −0.188, P = 0.038; Aβ+: β = −0.255, P = 0.038). Conclusion Plasma NRG1 concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD.

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“…Thus, we could not state that neurogranin is a specific biomarker of AD and further studies must be performed to assess whether neurogranin could be used as a biomarker for differential diagnosis among neurodegenerative diseases. Recently, Willemse et al showed that neurogranin did not differentiate AD from non-AD dementia in two dementia cohorts, one included clinical AD and non-AD patients with high CSF tau levels and the other included patients with a definite post-mortem diagnosis, independently from CSF biomarkers [ 34 ]. The authors concluded that neurogranin could reflect a general pathophysiological process of synaptic degeneration and it was not specific for AD.…”

Section: Discussionmentioning

confidence: 99%

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

et al. 2021

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(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological diseases (n = 70) and controls (33). We measured CSF neurogranin levels by a commercial ELISA kit. CSF RI of neurogranin was calculated by a robust method; (3) Results: AD patients showed increased levels of neurogranin. We also found that neurogranin was significantly correlated with T-tau, P-tau and mini mental state examination in AD patients. The lower and upper reference limits of the RI were 2.9 (90%CI 0.1–10.8) and 679 (90%CI 595–779), respectively; (4) Conclusion: This is the first study establishing the RI of CSF neurogranin.

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Neurogranin as biomarker in CSF is non-specific to Alzheimer's disease dementia

Cited by 16 publications

References 57 publications

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

Plasma neuregulin 1 as a synaptic biomarker in Alzheimer’s disease: a discovery cohort study

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

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