Diagnostic biomarkers of Alzheimer’s disease: A state-of-the-art review

Khoury, Rita; Ghossoub, Elias

doi:10.1016/j.bionps.2019.100005

Cited by 150 publications

(104 citation statements)

References 59 publications

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“…Similarly, a signature including all six biomarkers did not increase diagnostic performance. To date, the best diagnostic performance for AD has been reported for biomarkers detected in CSF [ 53 ]. This observation is not surprising, since CSF is in direct contact with brain interstitial fluid; therefore, biomarkers in CSF are specific of the brain and not diluted by others originating from different body districts (two conditions that characterize biomarkers detected in blood).…”

Section: Discussionmentioning

confidence: 99%

Uncharacterized RNAs in Plasma of Alzheimer’s Patients Are Associated with Cognitive Impairment and Show a Potential Diagnostic Power

Barbagallo

Martino

Grasso

et al. 2020

IJMS

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Alzheimer’s disease (AD) diagnosis is actually based on clinical evaluation and brain-imaging tests, and it can often be confirmed only post-mortem. Therefore, new non-invasive molecular biomarkers are necessary to improve AD diagnosis. As circulating microRNA biomarkers have been proposed for many diseases, including AD, we aimed to identify new diagnostic non-small RNAs in AD. Whole transcriptome analysis was performed on plasma samples of five AD and five unaffected individuals (CTRL) using the Clariom D Pico Assay, followed by validation in real-time PCR on 37 AD patients and 37 CTRL. Six differentially expressed (DE) transcripts were identified: GS1-304P7.3 (upregulated), NONHSAT090268, TC0100011037, TC0400008478, TC1400008125, and UBE2V1 (downregulated). Peripheral blood mononuclear cells (PBMCs) may influence the expression of circulating RNAs and their analysis has been proposed to improve AD clinical management. Accordingly, DE transcript expression was also evaluated in PBMCs, showing no difference between AD and CTRL. ROC (receiver operating characteristic) curve analysis was performed to evaluate the diagnostic accuracy of each DE transcript and a signature including all of them. A correlation between cognitive impairment and GS1-304P7.3, NONHSAT090268, TC0100011037, and TC0400008478 was detected, suggesting a potential association between their extracellular abundance and AD clinical phenotype. Finally, this study identified six transcripts showing altered expression in the plasma of AD patients. Given the need for new, accurate blood biomarkers for AD diagnosis, these transcripts may be considered for further analyses in larger cohorts, also in combination with other biomarkers, aiming to identify specific RNA-based biomarkers to be eventually applied to clinical practice.

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Section: Discussionmentioning

confidence: 99%

Uncharacterized RNAs in Plasma of Alzheimer’s Patients Are Associated with Cognitive Impairment and Show a Potential Diagnostic Power

Barbagallo

Martino

Grasso

et al. 2020

IJMS

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“…On the other hand, CSF analyses aim to provide quantitative measurements of Aβ and tau protein levels as AD biomarkers [ 18 ]. However, the available methods are expensive, relatively invasive [ 18 , 28 ], and have low sensitivity and specificity, which result in the risks of either overdiagnosis or undiagnosed, misattributed, or dismissed and ignored symptoms [ 29 , 30 ]. Additionally, as there is a serious lack of AD diagnosis assays at all illness stages, patients are generally diagnosed late, which places a great burden on the health systems [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Detection strategies based on novel biomarkers beyond Aβ and tau protein could represent a promising solution for the early diagnosis of AD [ 18 ]. However, as no single biomarker can be used to accurately diagnose AD, a combination of biomarkers could significantly increase diagnostic accuracy [ 30 , 31 ]. Moreover, such biomarkers should ideally be easy to sample and should be measurable through simple and cost-efficient methods and at all stages of the disease, allowing for standardization processes [ 30 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, as no single biomarker can be used to accurately diagnose AD, a combination of biomarkers could significantly increase diagnostic accuracy [ 30 , 31 ]. Moreover, such biomarkers should ideally be easy to sample and should be measurable through simple and cost-efficient methods and at all stages of the disease, allowing for standardization processes [ 30 , 32 ]. In this context, the aim of this manuscript is to provide an up-to-date overview of both conventional and novel AD biomarkers, which could play fundamental roles in its accurate and timely diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

2020

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Neurodegeneration is a highly complex process which is associated with a variety of molecular mechanisms related to ageing. Among neurodegenerative disorders, Alzheimer’s disease (AD) is the most common, affecting more than 45 million individuals. The underlying mechanisms involve amyloid plaques and neurofibrillary tangles (NFTs) deposition, which will subsequently lead to oxidative stress, chronic neuroinflammation, neuron dysfunction, and neurodegeneration. The current diagnosis methods are still limited in regard to the possibility of the accurate and early detection of the diseases. Therefore, research has shifted towards the identification of novel biomarkers and matrices as biomarker sources, beyond amyloid-β and tau protein levels within the cerebrospinal fluid (CSF), that could improve AD diagnosis. In this context, the aim of this paper is to provide an overview of both conventional and novel biomarkers for AD found within body fluids, including CSF, blood, saliva, urine, tears, and olfactory fluids.

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“…Combining information (multimodal) from different types of neuroimaging (structural and functional) with genotype (APOE) or biochemical (CSF) information, as do sMRI, AV45-PET, FDG-PET, DTI, and rs-fMRI, can help to improve diagnostic performance for AD or MCI compared with single-modality methods (Zhang et al, 2011;Young et al, 2013;Schouten et al, 2016;Wei et al, 2016;Gupta et al, 2019a). Furthermore, it has been noted lately that a combination of biomarkers yields a powerful diagnostic technique for classifying the AD group with cognitively healthy subjects, with specificity and sensitivity scores reaching above 90% (Bloudek et al, 2011;Rathore et al, 2017;Khoury and Ghossoub, 2019).…”

Section: Introductionmentioning

confidence: 99%

Classification and Graphical Analysis of Alzheimer’s Disease and Its Prodromal Stage Using Multimodal Features From Structural, Diffusion, and Functional Neuroimaging Data and the APOE Genotype

Gupta

Kim

et al. 2020

Front. Aging Neurosci.

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Classification of AD Using Six-Multi-Modalities on the basis of the 2-mm JHU-ICBM-labeled template atlas. To integrate the different modalities and different complementary information into one form, and to optimize the classifier, we used the multiple kernel learning (MKL) framework. The obtained results indicated that our multimodal approach yields a significant improvement in accuracy over any single modality alone. The areas under the curve obtained by the proposed method were 97.78, 96.94, 95.56, 96.25, 96.67, and 96.59% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs binary classification, respectively. Our proposed multimodal method improved the classification result for MCIs vs. MCIc groups compared with the unimodal classification results. Our study found that the (left/right) precentral region was present in all six binary classification groups (this region can be considered the most significant region). Furthermore, using nodal network topology, we found that FDG, AV45-PET, and rs-fMRI were the most important neuroimages, and showed many affected regions relative to other modalities. We also compared our results with recently published results.

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Diagnostic biomarkers of Alzheimer’s disease: A state-of-the-art review

Cited by 150 publications

References 59 publications

Uncharacterized RNAs in Plasma of Alzheimer’s Patients Are Associated with Cognitive Impairment and Show a Potential Diagnostic Power

Uncharacterized RNAs in Plasma of Alzheimer’s Patients Are Associated with Cognitive Impairment and Show a Potential Diagnostic Power

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

Classification and Graphical Analysis of Alzheimer’s Disease and Its Prodromal Stage Using Multimodal Features From Structural, Diffusion, and Functional Neuroimaging Data and the APOE Genotype

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