Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

Kester, Maartje I.; Teunissen, Charlotte E.; Crimmins, Daniel L.; Herries, Elizabeth M.; Ladenson, Jack H.; Scheltens, Philip; Flier, Wiesje M. van der; Morris, John C.; Holtzman, David M.; Fagan, Anne M.

doi:10.1001/jamaneurol.2015.1867

Cited by 201 publications

(197 citation statements)

References 31 publications

Supporting

Mentioning

165

Contrasting

Order By: Relevance

“…Owing to the cross-sectional nature of the study, it was not possible to differentiate stable-MCI subjects from those progressing and converting into dementia. Further studies are needed to confirm the potential value of neurogranin in predicting conversion from MCI to AD [17,18]. Extensive psychometric data were not available in our study, thus preventing the study of CSF neurogranin concentrations in relation to different cognitive dimensions.…”

Section: Discussionmentioning

confidence: 90%

“…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%

See 1 more Smart Citation

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

Lista¹,

Toschi

Baldacci

et al. 2017

JAD

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

Lista¹,

Toschi

Baldacci

et al. 2017

JAD

View full text Add to dashboard Cite

show abstract

“…Nrgn had recently been suggested as cerebrospinal fluid biomarker for AD (36,37). Forced expression of Nrgn enhances local synaptic plasticity in mice (38).…”

Section: Discussionmentioning

confidence: 99%

An N-terminal motif unique to primate tau enables differential protein–protein interactions

Stefanoska

Volkerling

Bertz

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Compared with other mammalian species, humans are particularly susceptible to taumediated neurodegenerative disorders. Differential interactions of the tau protein with other proteins are critical for mediating tau's physiological functions as well as tauassociated pathological processes. Primate tau harbors an 11-amino-acid-long motif in its Nterminal region (residues 18-28), which is not present in non-primate species and whose function is unknown. Here, we used deletion mutagenesis to remove this sequence region from the longest human tau isoform, followed by glutathione-S transferase (GST) pulldown assays paired with isobaric tags for relative and absolute quantitation (iTRAQ) multiplex labeling, a quantitative method to measure protein abundance by mass spectrometry.

show abstract

“…It is a postsynaptic protein that is mainly expressed in the cortex and hippocampus, where it is concentrated in dendritic spines, and has a major role in regulating LTP and learning. Cerebrospinal (CSF) Ng is elevated in patients fulfilling clinical criteria for AD compared to mild cognitive impairment (MCI) patients as well as controls, a finding that has been replicated using different assays and across clinical sites 4, 5, 6, 7. Importantly, it has not yet been determined if it is also elevated in atypical forms of AD.…”

Section: Introductionmentioning

confidence: 99%

CSF neurogranin or tau distinguish typical and atypical Alzheimer disease

Wellington¹,

Paterson

Suárez‐González

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveTo assess whether high levels of cerebrospinal fluid neurogranin are found in atypical as well as typical Alzheimer's disease.MethodsImmunoassays were used to measure cerebrospinal fluid neurogranin in 114 participants including healthy controls (n = 27), biomarker‐proven amnestic Alzheimer's disease (n = 68), and the atypical visual variant of Alzheimer's (n = 19) according to international criteria. CSF total‐tau, Aβ42, and neurofilament light concentrations were investigated using commercially available assays. All affected individuals had T1‐weighted volumetric MR images available for analysis of whole and regional brain volumes. Associations between neurogranin, brain volumes, total‐tau, Aβ42, and neurofilament light were assessed.ResultsMedian cerebrospinal fluid neurogranin concentrations were higher in typical and atypical Alzheimer's compared to controls (P < 0.001 and P = 0.005). Both neurogranin and total‐tau concentrations, but not neurofilament light and Aβ42, were higher in typical Alzheimer's compared to atypical patients (P = 0.004 and P = 0.03). There were significant differences in the left hippocampus and right and left superior parietal lobules in atypical patients, which were larger (P = 0.03) and smaller (P = 0.001 and P < 0.001), respectively, compared to typical patients. We found no evidence of associations between neurogranin and brain volumes but a strong association with total‐tau (P < 0.001) and a weaker association with neurofilament light (P = 0.005).InterpretationThese results show significant differences in neurogranin and total‐tau between typical and atypical patients, which may relate to factors other than disease topography. The differential relationships between neurogranin, total‐tau and neurofilament light in the Alzheimer's variants, provide evidence for mechanistically distinct and coupled markers of neurodegeneration.

show abstract

Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

Cited by 201 publications

References 31 publications

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

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

An N-terminal motif unique to primate tau enables differential protein–protein interactions

CSF neurogranin or tau distinguish typical and atypical Alzheimer disease

Contact Info

Product

Resources

About