Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease

Kvartsberg, Hlin; Duits, Flora H.; Ingelsson, Martin; Andreasen, Niels; Öhrfelt, Annika; Andersson, Kerstin; Brinkmalm, Gunnar; Lannfelt, Lars; Minthon, Lennart; Hansson, Oskar; Andréasson, Ulf; Teunissen, Charlotte E.; Scheltens, Philip; Flier, Wiesje M. van der; Zetterberg, Henrik; Portelius, Erik; Blennow, Kaj

doi:10.1016/j.jalz.2014.10.009

Cited by 266 publications

(317 citation statements)

References 38 publications

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“…Our findings suggest that the proposition that synaptic markers can predict cognitive decline in AD [33], should be extended to Lewy body diseases. Finally, the relationship of Rab3A and SNAP25 to disease pathology and impact on cognitive decline highlights their importance as a treatment target and its potential as a future biomarker of disease progression for clinical trials is a path that should be further explored.…”

Section: Conclusion and Future Implicationsmentioning

confidence: 74%

Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

Bereczki

Francis

Howlett

et al. 2016

Alzheimer's & Dementia

136

104

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METHODS: 129 post-mortem human brain samples were analyzed in brain regional specific manner exploring their associations with morphological changes and cognitive decline.RESULTS: We have observed robust changes reflecting synaptic dysfunction in all studied dementia groups. There were significant associations between the rate of cognitive decline and decreased levels of Rab3 in DLB in the inferior parietal lobe and SNAP25 in AD in the prefrontal cortex. Of particular note, synaptic proteins significantly discriminated between dementia cases and controls with over 90% sensitivity and specificity. DISCUSSION: Our findings suggest that the proposition that synaptic markers can predict cognitive decline in AD, should be extended to Lewy body diseases.

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Section: Conclusion and Future Implicationsmentioning

confidence: 74%

Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

Bereczki

Francis

Howlett

et al. 2016

Alzheimer's & Dementia

136

104

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“…CSF neurogranin concentration was measured using a previously described in‐house ELISA 6. Briefly, an assay based on the monoclonal antibody Ng7 (epitope including amino acids 52–65 on neurogranin) was used for capture, a polyclonal neurogranin anti‐rabbit antibody (ab23570; Upstate Biotechnology, Lake Placid, NY, USA) for detection, and full‐length neurogranin protein as calibrator.…”

Section: Methodsmentioning

confidence: 99%

Impaired synaptic function is linked to cognition in Parkinson's disease

Selnes

Stav

Johansen

et al. 2017

Ann Clin Transl Neurol

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ObjectiveCognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐β, and presynaptic deposits of α‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐β, and the synapse related‐markers CSF neurogranin and α‐synuclein.MethodsThirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years).ResultsAll subjects had CSF amyloid‐β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, α‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐β and α‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group.Interpretation CSF Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease.

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“…All CSF neurogranin analyses were performed at the Clinical Neurochemistry Laboratory at the Sahlgrenska University Hospital (Mölndal, Sweden) using a previously described analytical methodology [13]. In short, CSF neurogranin was measured using an in-house ELISA assay based on the monoclonal antibody Ng7 (epitope including amino acids 52-65 on neurogranin) for capture, a polyclonal neurogranin anti-rabbit antibody (ab23570; Upstate Biotechnology, Lake Placid, NY, USA) for detection, and full-length neurogranin protein as calibrator.…”

Section: Immunoassay For Csf Neurograninmentioning

confidence: 99%

“…Compared with healthy controls (HC), cerebrospinal fluid (CSF) neurogranin concentrations are increased in patients with AD [13][14][15] and subjects with mild cognitive impairment (MCI) as well as MCI progressors and converters to AD (MCI-AD) [13,16]. Moreover, neurogranin predicts progression from MCI to AD dementia [13,17,18] and rate of cognitive decline [13], and correlates longitudinally with rates of hippocampal atrophy [18,19] as well as with reduced regional cortical glucose metabolism assessed by 18 F-Fluorodeoxyglucosepositron emission tomography ( 18 F-FDG-PET) [18]. Very recently, CSF profiling of the human brain enriched proteome has confirmed a significant association between increased neurogranin concentrations and AD [20].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study

Lista¹,

Toschi

Baldacci

et al. 2017

JAD

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Abstract. We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35) S. Lista et al. / CSF Neurogranin in Neurodegenerative Diseasescognitively HC (n = 23)]. CSF neurogranin concentrations were significantly higher in AD patients compared with both HC subjects and FTD patients, suggesting that increased CSF neurogranin concentrations may indicate AD-related pathophysiology. CSF neurogranin was independently associated with both total tau and hyperphosphorylated tau proteins, whereas a non-significant correlation with the 42-amino acid-long amyloid-␤ peptide was evident. CSF neurogranin, however, was not superior to core AD biomarkers in differentiating HC from the three diagnostic groups, and it did not improve their diagnostic accuracy. We conclude that further classification and longitudinal studies are required to shed more light into the potential role of neurogranin as a pathophysiological biomarker of neurodegenerative diseases.

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Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease

Abstract: These results suggest that CSF Ng is a novel AD biomarker that may be used to monitor synaptic degeneration, and correlates with the rate of cognitive decline in prodromal AD.

Cited by 266 publications

References 38 publications

Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

Impaired synaptic function is linked to cognition in Parkinson's disease

Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study

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