Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

Giau, Vo Van; Bagyinszky, Eva; An, Seong Soo A.

doi:10.3390/ijms20174149

Cited by 67 publications

(48 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CSF or blood biomarkers lead the effort to enable more effective DMTs. Their context of use in clinical trials includes patient selection, patient's classification in a disease state, clarification of therapeutic agent's mechanism of action, appropriate dose selection and measurement of treatment response [34].…”

Section: Inadequate Understanding Of the Complex Pathophysiology Of Amentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Inadequate Understanding Of the Complex Pathophysiology Of Amentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Great efforts have been made to explore diagnostic and screening tools for aMCI, such as psychological batteries (2,4,5), cerebrospinal fluid biomarkers (6), and molecular imaging approaches (7). These methods have their special strengths and limitations.…”

Section: Introductionmentioning

confidence: 99%

Changes in Brain Function Networks in Patients With Amnestic Mild Cognitive Impairment: A Resting-State fMRI Study

Wang

Liu

et al. 2020

Front. Neurol.

View full text Add to dashboard Cite

Patients with amnestic mild cognitive impairment (aMCI) are at high risk of developing dementia. This study used resting-state functional magnetic resonance imaging (rs-fMRI) and an independent component analysis (ICA) approach to explore changes in functional connectivity (FC) in the default mode network (DMN), executive control network (ECN), and salience network (SN). Thirty patients with aMCI and 30 healthy controls (HCs) were enrolled. All the participants underwent an rs-fMRI scan. The brain FC in DMN, ECN, and SN was calculated using the ICA approach. We found that the FC of brain regions in DMN decreased significantly and that of brain regions in ECN increased, which was in accordance with the findings of previous studies on Alzheimer's disease (AD) and aMCI. We also found that the FC of brain regions in SN increased, which was different from the findings of previous studies on AD. The increase in FC in brain regions in SN might result from different pathophysiological states in AD and aMCI, indicating that a decrease in FC in SN does not occur in a person with aMCI. These results are consistent with those of previous studies using the voxel-mirrored homotopic connectivity approach and seed-based correlation analysis. We therefore considered that the decrease in FC in DMN and the increase in FC in ECN and SN might be peculiar patterns observed on the rs-fMRI of a person with aMCI. These findings may contribute to the development of imaging biomarkers for the diagnosis of aMCI.

show abstract

“…However, early disease diagnosis may be problematic; patients with dementia are usually diagnosed 2-3 years after the first symptoms appeared, and cases have remained undiagnosed/misdiagnosed. Further studies are needed on biomarkers, which could enhance accuracy AD diagnosis during the lifetime [86,130]. Studying transcriptomes may provide additional markers (DEGs, non-coding RNAs) that improve the diagnosis of AD.…”

Section: Challenges and Future Insightsmentioning

confidence: 99%

“…In addition, mRNA from blood may be unstable, and it could be difficult to get samples from human brain species [132]. Peripheral samples (peripheral blood, serum, plasma, or peripheral blood mononuclear cells) could be more accessible for searching AD biomarkers as well as mild cognitive impairment [130]. Studying the transcriptomic signature of blood may be a useful approach in for AD prediction and in early disease diagnosis [133].…”

Section: Challenges and Future Insightsmentioning

confidence: 99%

Transcriptomics in Alzheimer’s Disease: Aspects and Challenges

Bagyinszky

Giau

2020

IJMS

Self Cite

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common cause of dementia. Although the heritability of AD is high, the knowledge of the disease-associated genes, their expression, and their disease-related pathways remain limited. Hence, finding the association between gene dysfunctions and pathological mechanisms, such as neuronal transports, APP processing, calcium homeostasis, and impairment in mitochondria, should be crucial. Emerging studies have revealed that changes in gene expression and gene regulation may have a strong impact on neurodegeneration. The mRNA–transcription factor interactions, non-coding RNAs, alternative splicing, or copy number variants could also play a role in disease onset. These facts suggest that understanding the impact of transcriptomes in AD may improve the disease diagnosis and also the therapies. In this review, we highlight recent transcriptome investigations in multifactorial AD, with emphasis on the insights emerging at their interface.

show abstract

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

Cited by 67 publications

References 152 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

Changes in Brain Function Networks in Patients With Amnestic Mild Cognitive Impairment: A Resting-State fMRI Study

Transcriptomics in Alzheimer’s Disease: Aspects and Challenges

Contact Info

Product

Resources

About