A meta-analysis on CSF neurogranin levels for the diagnosis of Alzheimer’s disease and mild cognitive impairment

Mavroudis, Ioannis; Petridis, Foivos; Chatzikonstantinou, Symela; Kazis, Dimitrios

doi:10.1007/s40520-019-01326-z

Cited by 38 publications

(38 citation statements)

References 24 publications

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“…It is involved in long-term potentiation and memory consolidation [2]. It has been shown to predict disease progression in several studies, even in cognitively normal controls [47,48]. Its levels are correlated with brain atrophy in subjects with Aβ pathology and with rapid cognitive deterioration during clinical follow-up [2].…”

Section: Novel Biomarkers For Synaptic Dysfunctionmentioning

confidence: 99%

Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research

et al. 2019

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Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and Cerebrospinal fluid (CSF) biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are assessed in clinical trials. The above-mentioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are relevant to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

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Section: Novel Biomarkers For Synaptic Dysfunctionmentioning

confidence: 99%

Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research

et al. 2019

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“…Further, within the progressive MCI group, elevated CSF Ng levels correlate with accelerated deterioration in Alzheimer’s disease Assessment Scale—cognitive subscale ( Portelius et al, 2015 ). In a recent meta-analysis, it revealed that the CSF Ng level is significantly higher in MCI patients progressed to AD than that in stable MCI patients ( Mavroudis et al, 2019 ).…”

Section: Associations Between Neurogranin and Neurological And Mentalmentioning

confidence: 99%

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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“…While Kvartsberg et al, 2019 reported a decrease of neurogranin in the brain of AD patients [103], several other studies have reported an increase of neurogranin in CSF of AD patients [79,88,95,[104][105][106]157]. CSF neurogranin levels did not significantly differ between AD patients and patients with Lewy body dementia (LBD) [158]. In contrast, Mavroudis et al, 2019 found that CSF levels of neurogranin were significantly higher in AD patients compared with cognitively normal participants, as well as between AD patients and patients with mild cognitive impairment (MCI), So, AD patients have higher neurogranin levels compared to MCI , and MCI has higher neurogranin levels compared to controls, which indicates that neurogranin levels might be used to differentiate MCI patients from AD patients [158].…”

Section: Neurograninmentioning

confidence: 92%

“…CSF neurogranin levels did not significantly differ between AD patients and patients with Lewy body dementia (LBD) [158]. In contrast, Mavroudis et al, 2019 found that CSF levels of neurogranin were significantly higher in AD patients compared with cognitively normal participants, as well as between AD patients and patients with mild cognitive impairment (MCI), So, AD patients have higher neurogranin levels compared to MCI , and MCI has higher neurogranin levels compared to controls, which indicates that neurogranin levels might be used to differentiate MCI patients from AD patients [158]. In blood, no significant change in neurogranin concentration has been detected in AD compared to controls [95,105].…”

Section: Neurograninmentioning

confidence: 98%

Utility of Animal Models to Understand Human Alzheimer’s Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals

Qin

Prins

Groeneveld

et al. 2020

IJMS

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To diagnose and treat early-stage (preclinical) Alzheimer’s disease (AD) patients, we need body-fluid-based biomarkers that reflect the processes that occur in this stage, but current knowledge on associated processes is lacking. As human studies on (possible) onset and early-stage AD would be extremely expensive and time-consuming, we investigate the potential value of animal AD models to help to fill this knowledge gap. We provide a comprehensive overview of processes associated with AD pathogenesis and biomarkers, current knowledge on AD-related biomarkers derived from on human and animal brains and body fluids, comparisons of biomarkers obtained in human AD and frequently used animal AD models, and emerging body-fluid-based biomarkers. In human studies, amyloid beta (Aβ), hyperphosphorylated tau (P-tau), total tau (T-tau), neurogranin, SNAP-25, glial fibrillary acidic protein (GFAP), YKL-40, and especially neurofilament light (NfL) are frequently measured. In animal studies, the emphasis has been mostly on Aβ. Although a direct comparison between human (familial and sporadic) AD and (mostly genetic) animal AD models cannot be made, still, in brain, cerebrospinal fluid (CSF), and blood, a majority of similar trends are observed for human AD stage and animal AD model life stage. This indicates the potential value of animal AD models in understanding of the onset and early stage of AD. Moreover, animal studies can be smartly designed to provide mechanistic information on the interrelationships between the different AD processes in a longitudinal fashion and may also include the combinations of different conditions that may reflect comorbidities in human AD, according to the Mastermind Research approach.

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A meta-analysis on CSF neurogranin levels for the diagnosis of Alzheimer’s disease and mild cognitive impairment

Cited by 38 publications

References 24 publications

Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research

Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research

Neurogranin: A Potential Biomarker of Neurological and Mental Diseases

Utility of Animal Models to Understand Human Alzheimer’s Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals

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