Alzheimer's disease biomarkers: another tool for FAA pilot screening?
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ABSTRACT:
SUBMITTER: Lawrence MW
PROVIDER: S-EPMC6813941 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Novel biomarkers are important for identifying as well as differentiating subcortical vascular dementia (SVD) and Alzheimer's disease (AD) at an early stage in the disease process. METHODS: In two independent cohorts, a multiplex immunoassay was utilized to analyze 90 proteins in cerebrospinal fluid (CSF) samples from dementia patients and patients at risk of developing dementia (mild cognitive impairment). RESULTS: The levels of several CSF proteins were increased in SVD and its incipient state, and in moderate-to-severe AD compared with the control group. In contrast, some CSF proteins were altered in AD, but not in SVD. The levels of heart-type fatty acid binding protein (H-FABP) were consistently increased in all groups with dementia but only in some of their incipient states. CONCLUSIONS: In summary, these results support the notion that SVD and AD are driven by different pathophysiological mechanisms reflected in the CSF protein profile and that H-FABP in CSF is a general marker of neurodegeneration.
| S-EPMC3199889 | biostudies-other
Project description:The adaptive immune system is thought to be a rich source of protein biomarkers, but diagnostically useful antibodies remain unknown for a large number of diseases. This is, in part, because the antigens that trigger an immune response in many diseases remain unknown. We present here a general and unbiased approach to the identification of diagnostically useful antibodies that avoids the requirement for antigen identification. This method involves the comparative screening of combinatorial libraries of unnatural, synthetic molecules against serum samples obtained from cases and controls. Molecules that retain far more IgG antibodies from the case samples than the controls are identified and subsequently tested as capture agents for diagnostically useful antibodies. The utility of this method is demonstrated using a mouse model for multiple sclerosis and via the identification of two candidate IgG biomarkers for Alzheimer's disease.
| S-EPMC3066439 | biostudies-literature
Project description:Cognitive screening is often a first step to document cognitive status of patients suspected having Alzheimer's disease (AD). Unfortunately, screening neuropsychological tests are often insensitivity in the detection. The goal of this study was to develop a simple and sensitive screening neuropsychological test to facilitate early detection of AD. This study recruited 761 elderly individuals suspected of having AD and presenting various cognitive statuses (mean age: 77.69 ± 8.45 years; proportion of females: 65%; cognitively unimpaired, CU, n = 133; mild cognitive impairment, MCI, n = 231; dementia of Alzheimer's type, DAT, n = 397). This study developed a novel screening neuropsychological test incorporating assessments of the core memory deficits typical of early AD and an interview on memory function with an informant. The proposed History-based Artificial Intelligence-Show Chwan Assessment of Cognition (HAI-SAC) was assessed in terms of psychometric properties, test time, and discriminative ability. The results were compared with those obtained using other common screening tests, including Cognitive Abilities Screening Instrument (CASI), Montreal Cognitive Assessment (MoCA), and an extracted Mini-Mental State Examination score from CASI. HAI-SAC demonstrated acceptable internal consistency. Factor analysis revealed two factors: memory (semantic and contextual) and cognition-related information from informants. The assessment performance of HAI-SAC was strongly correlated with that of the common screening neuropsychological tests addressed in this study. HAI-SAC outperformed the other tests in differentiating CU individuals from patients with MCI (sensitivity: 0.87; specificity: 0.58; area under the curve [AUC]: 0.78) or DAT (sensitivity: 0.99; specificity: 0.89; AUC: 0.98). Performance of HAI-SAC on differentiating MCI from DAT was on par with performances of other tests (sensitivity: 0.78; specificity: 0.84; AUC: 0.87), while the test time was less than one quarter that of CASI and half that of MoCA. HAI-SAC is psychometrically sound, cost-effective, and sensitive in discriminating the cognitive status of AD.
| S-EPMC9836308 | biostudies-literature
Project description:Alzheimer's disease (AD) is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to find specific biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and inflammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid (CSF) biomarkers (β-amyloid, total tau, and hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.
| S-EPMC5562658 | biostudies-other
Project description:ObjectiveTo report and evaluate a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors.DesignProspective case cohort comparative study.SettingStroke units at two secondary care hospitals and one tertiary centre.Participants116 stroke survivors were screened, 62 by naïve and 54 by non-naïve screeners.Main outcome measuresBoth the VISA screening tool and the comprehensive specialist vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention.ResultsFull completion of VISA tool and specialist vision assessment was achieved for 89 stroke survivors. Missing data for one or more sections typically related to patient's inability to complete the assessment. Sensitivity and specificity of the VISA screening tool were 90.24% and 85.29%, respectively; the positive and negative predictive values were 93.67% and 78.36%, respectively. Overall agreement was significant; k=0.736. Lowest agreement was found for screening of eye movement and visual inattention deficits.ConclusionsThis early validation of the VISA screening tool shows promise in improving detection accuracy for clinicians involved in stroke care who are not specialists in vision problems and lack formal eye training, with potential to lead to more prompt referral with fewer false positives and negatives. Pilot validation indicates acceptability of the VISA tool for screening of visual impairment in stroke survivors. Sensitivity and specificity were high indicating the potential accuracy of the VISA tool for screening purposes. Results of this study have guided the revision of the VISA screening tool ahead of full clinical validation.
| S-EPMC5855179 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a distinctive type of endogenous non-coding RNAs, and their regulatory roles in neurological disorders have received immense attention. CircRNAs significantly contribute to the regulation of gene expression and progression of neurodegenerative disorders including Alzheimer's disease (AD). The current study aimed to identify circRNAs as prognostic and potential biomarkers in AD. The differentially expressed circRNAs among subjective cognitive decline, amnestic mild cognitive impairment, and age-matched normal donors were determined through Arraystar Human circRNA Array V2 analysis. The annotations of circRNAs-microRNA interactions were predicted by employing Arraystar's homemade microRNAs (miRNA) target prediction tool. Bioinformatics analyses comprising gene ontology enrichment, KEGG pathway, and network analysis were conducted. Microarray analysis revealed the 33 upregulated and 11 downregulated differentially expressed circRNAs (FC ≥ 1.5 and p-values ≤ 0.05). The top 10 differentially expressed upregulated and downregulated circRNAs have been chosen for further expression validation through quantitative real-time PCR and subsequently, hsa-circRNA_001481 and hsa_circRNA_000479 were confirmed experimentally. Bioinformatics analyses determined the circRNA-miRNA-mRNA interactions and microRNA response elements to inhibit the expression of miRNAs and mRNA targets. Gene ontology enrichment and KEGG pathways analysis revealed the functional clustering of target mRNAs suggesting the functional verification of these two promising circRNAs. It is concluded that human circRNA_001481 and circRNA_000479 could be utilized as potential biomarkers for the early onset detection of AD and the development of effective therapeutics.
| S-EPMC9296062 | biostudies-literature
Project description:BackgroundAlzheimer's disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest.ObjectiveThis study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development.MethodsUrinary cytokine concentrations were measured in AD (n = 25), MCI (n = 25), and NC (n = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD.ResultsSignificant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59-0.79, sensitivity: 0.72-0.80, specificity: 0.56-0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors.ConclusionThis study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility.
| S-EPMC10357120 | biostudies-literature
Project description:BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterised by cognitive decline, behavioural and psychological symptoms of dementia (BPSD) and impairment of activities of daily living (ADL). Early differentiation of AD from mild cognitive impairment (MCI) is necessary.MethodsA total of 458 patients newly diagnosed with AD and MCI were included. Eleven batteries were used to evaluate ADL, BPSD and cognitive function (ABC). Machine learning approaches including XGboost, classification and regression tree, Bayes, support vector machines and logical regression were used to build and verify the new tool.ResultsThe Alzheimer's Disease Assessment Scale (ADAS-cog) word recognition task showed the best importance in judging AD and MCI, followed by correct numbers of auditory verbal learning test delay recall and ADAS-cog orientation. We also provided a selected ABC-Scale that covered ADL, BPSD and cognitive function with an estimated completion time of 18 min. The sensitivity was improved in the four models.ConclusionThe quick screen ABC-Scale covers three dimensions of ADL, BPSD and cognitive function with good efficiency in differentiating AD from MCI.
| S-EPMC10729043 | biostudies-literature
Project description:The role of hyperphosphorylation of the microtubule-associated protein tau in the pathological processes of several neurodegenerative diseases is becoming better understood. Consequently, development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. For this reason, dependable in vitro and in vivo models that reflect tau hyperphosphorylation in human diseases are needed. In this study, we generated and validated an in vitro model appropriate to test potential curative and preventive compound effects on tau phosphorylation. For this purpose, a stably transfected SH-SY5Y cell line was constructed over-expressing mutant human tau441 (SH-SY5Y-TMHT441). Analyses of expression levels and tau phosphorylation status in untreated cells confirmed relevance to human diseases. Subsequently, the effect of different established kinase inhibitors on tau phosphorylation (e.g., residues Thr231, Thr181, and Ser396) was examined. It was shown with several methods including immunosorbent assays and mass spectrometry that the phosphorylation pattern of tau in SH-SY5Y-TMHT441 cells can be reliably modulated by these compounds, specifically targeting JNK, GSK-3, CDK1/5, and CK1. These four protein kinases are known to be involved in in vivo tau phosphorylation and are therefore authentic indicators for the suitability of this new cell culture model for tauopathies.
| S-EPMC3323815 | biostudies-literature
Project description:BACKGROUND Alzheimer's disease (AD) is the leading cause of dementia worldwide; however, the molecular mechanisms underlying its pathogenesis remain unclear. The present study aimed to discover some potential peripheral blood biomarkers for early detection of patients with AD. MATERIAL AND METHODS Publicly available AD datasets - GSE18309 and GSE97760 - were obtained from the Gene Expression Omnibus database, and limma package from Bioconductor was employed to search for differently expressed genes (DEGs). Weighted correlation network analysis was performed to identify DEGs with highly synergistic changes, and functional annotation of DEGs was performed using gene set enrichment analysis and Metascape. STRING and Cytoscape were used to construct protein-protein interaction networks and analyze the most significant hub genes. Thereafter, the Comparative Toxicogenomics Database (CTD) was used to identify hub genes associated with AD pathology, and Connectivity Map was used to screen small molecule drugs for AD. Finally, hub genes coupled with corresponding predicted miRNAs involved in AD were assessed via TargetScan, and functional annotation of predicted miRNAs was performed using DIANA database. RESULTS Our analyses revealed 5042 DEGs; based on functional analyses, these DEGs were mainly associated with oligosaccharide lipid intermediate biosynthetic process, cyclin binding, signaling pathways regulating pluripotency of ubiquitin mediated proteolysis, and extracellular matrix-receptor interaction. UBB, UBA52, SRC, MMP9, VWF, GP6, and PF4 were identified as the hub genes. The CTD showed that these hub genes are closely related with AD or cognition impairment. CONCLUSIONS The identified hub genes and corresponding miRNAs might be useful as potential peripheral blood biomarkers of AD.
| S-EPMC7453750 | biostudies-literature