C‐terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer's disease

Vos, Ann De; Jacobs, Dirk; Struyfs, Hanne; Fransén, Erik; Andersson, Kerstin; Portelius, Erik; Andréasson, Ulf; Surgeloose, Didier De; Hernalsteen, Daniëlle; Sleegers, Kristel; Robberecht, Caroline; Broeckhoven, Christine Van; Zetterberg, Henrik; Blennow, Kaj; Engelborghs, Sebastiaan; Vanmechelen, Eugeen

doi:10.1016/j.jalz.2015.05.012

Cited by 132 publications

(122 citation statements)

References 42 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…They are linked to the disruption of amyloid metabolism and plaque pathology, and to the cortical neurodegeneration occurring in the disease [39]. Since levels of neurogranin are increased in the CSF of AD patients, while they are decreased in AD brains, this protein has also been discussed as a potential AD biomarker [17, 18, 19, 20, 21, 22]. Moreover, studies have suggested that neurogranin might be an AD-specific biomarker.…”

Section: Discussionmentioning

confidence: 99%

“…This can indirectly be observed by measuring levels of the postsynaptic protein neurogranin in brain tissue [10, 11, 12]. Decreased levels of neurogranin, a protein that has a key role in long-term potentiation and learning [13, 14, 15], have been found in brains of AD patients [10, 16], while CSF neurogranin levels are increased [17, 18, 19, 20]. Studies have suggested that increased CSF neurogranin levels might even be predictive of progression from MCI to AD; thus, this protein has also been discussed as a potential AD biomarker [21, 22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer’s Disease: A Pilot Study

Schipke

Vos²,

Fuentes

et al. 2018

Dement Geriatr Cogn Disord Extra

Self Cite

View full text Add to dashboard Cite

Background/Aims: Major depressive disorder (MDD) can cooccur with early Alzheimer’s disease (AD) or may cause memory problems independently of AD. Previous studies have suggested that the AD-related cerebrospinal fluid (CSF) biomarkers tau and Aβ(1–42) could help discriminate between early AD and depression unrelated to AD. Moreover, the postsynaptic protein neurogranin and presynaptic BACE1 have increasingly gained attention as potential new AD biomarkers, but they have not yet been investigated concerning depression. Methods: Using ELISAs, we studied CSF neurogranin and BACE1 levels in patients with mild (n = 21) and moderate (n = 19) AD, as well as in MDD patients with (n = 20) and without (n = 20) cognitive deficits. The clinical examinations included analyses of t-tau, Aβ(1–42), and Aβ(1–40), besides neuropsychological tests and cranial magnetic resonance imaging. Depressive symptom severity was assessed using the Geriatric Depression Scale (GDS). Results: Along with classic AD biomarkers, neurogranin and BACE1 CSF levels differed between moderate AD and MDD (p ≤ 0.01). MDD associated with cognitive deficits was distinguished from mild AD through the CSF neurogranin/BACE1 ratio (p < 0.05), which was strongly correlated with GDS scores (ρ = –0.656; p < 0.01). Conclusion: The neurogranin/BACE1 ratio in CSF can distinguish between depression and AD among patients with similar cognitive deficits, along with the classic AD biomarkers. Further longitudinal studies are ongoing to identify which biomarkers have prognostic value.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer’s Disease: A Pilot Study

Schipke

Vos²,

Fuentes

et al. 2018

Dement Geriatr Cogn Disord Extra

Self Cite

View full text Add to dashboard Cite

show abstract

“…CSF neurogranin levels are higher in AD [63, 175, 190, 221, 242, 291, 310, 347, 354, 361] or MCI patients [291, 347] compared with controls or non-AD dementia patients [354]. Higher levels of CSF neurogranin have been reported in AD compared with MCI [138, 291], although there was no significant difference between AD and MCI Aβ-positive (based on CSF Aβ42) groups in a recent study of the ADNI cohort [347].…”

Section: Synaptic Dysfunctionmentioning

confidence: 99%

“…To date, no significant differences have been reported in plasma levels of neurogranin between patients with AD and controls [63, 190]. However, levels of neurogranin in neuronally derived exosomes in plasma have been found to be lower in AD patients compared with controls [110, 389], as well as in MCI subjects who progressed to AD compared with stable MCI subjects [389].…”

Section: Synaptic Dysfunctionmentioning

confidence: 99%

Current state of Alzheimer’s fluid biomarkers

et al. 2018

Self Cite

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

show abstract

“…Synaptic loss has been reported to occur very early in the natural history of AD, therefore neurogranin can be a valuable biomarker of early, possible preclinical, stage of the disease [23]. Neurogranin concentrations are significantly increased in mild cognitive impairment (MCI) [24, 25] and can be a predictive factor of conversion to dementia.…”

Section: Introductionmentioning

confidence: 99%

No diurnal variation of classical and candidate biomarkers of Alzheimer’s disease in CSF

Cicognola

Chiasserini

Andréasson

et al. 2016

Mol Neurodegeneration

Self Cite

View full text Add to dashboard Cite

BackgroundCerebrospinal fluid (CSF) biomarkers have gained increasing importance in the diagnostic work-up of Alzheimer’s disease (AD). The core CSF biomarkers related to AD pathology (Aβ42, t-tau and p-tau) are currently used in CSF diagnostics, while candidate markers of amyloid metabolism (Aβ38, Aβ40, sAPPα, sAPPβ), synaptic loss (neurogranin), neuroinflammation (YKL-40), neuronal damage (VILIP-1) and genetic risk (apolipoprotein E) are undergoing evaluation. Diurnal fluctuation in the concentration of CSF biomarkers has been reported and may represent a preanalytical confounding factor in the laboratory diagnosis of AD. The aim of the present study was to investigate the diurnal variability of classical and candidate CSF biomarkers in a cohort of neurosurgical patients carrying a CSF drainage.MethodSamples were collected from a cohort of 13 neurosurgical patients from either ventricular (n = 6) or lumbar (n = 7) CSF drainage at six time points during the day, 1–7 days following the neurosurgical intervention. Concentrations of the core biomarkers were determined by immunoassays.ResultsAlthough absolute values largely varied among subjects, none of the biomarkers showed significant diurnal variation. Site of drainage (lumbar vs. ventricular) did not influence this result. The different immunoassays used for tau and Aβ markers provided similar results.ConclusionTime of day at CSF collection does not ultimately affect the concentration levels of classical and candidate AD biomarkers. Similar trends were found when using different immunoassays, thus corroborating the consistency of the data.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0130-3) contains supplementary material, which is available to authorized users.

show abstract

C‐terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer's disease

Abstract: This study strengthens the potential of neurogranin as an AD CSF biomarker, which now needs validation in larger studies. As tools, straightforward immunoassays can be used, as demonstrated by the described ELISA.

Cited by 132 publications

References 42 publications

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer’s Disease: A Pilot Study

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer’s Disease: A Pilot Study

Current state of Alzheimer’s fluid biomarkers

No diurnal variation of classical and candidate biomarkers of Alzheimer’s disease in CSF

Contact Info

Product

Resources

About