scholarly journals Small nucleolar RNAs in plasma and their discriminatory power as diagnostic biomarkers of Alzheimer's disease

2021 ◽  
Author(s):  
Nicholas F Fitz ◽  
Kyong Nyon Nam ◽  
Jiebiao Wang ◽  
M. Ilyas Kamboh ◽  
Radosveta Koldamova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Discriminatory Power ◽  
Diagnostic Process ◽  
Rna Seq ◽  
Diagnostic Biomarkers ◽  
Significant Enrichment ◽  
High Discriminatory Power ◽  
Nucleolar Rnas

The clinical diagnosis of Alzheimer's disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ; peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs - a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs - SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.

scholarly journals Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

2021 ◽  
Author(s):  
Liu-Lin Xiong ◽  
Lu-Lu Xue ◽  
Ruo-Lan Du ◽  
Rui-Ze Niu ◽  
Li Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Early Stage ◽  
Diagnostic Process ◽  
Sequencing Analysis ◽  
Single Cell Rna Sequencing

AbstractIn recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

scholarly journals Non-Invasive Diagnostic Biomarkers for Alzheimer’s Disease

2021 ◽  
Vol 3 (1) ◽  
pp. 12-18
Author(s):  
Shyamasri Biswas ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Success ◽  
Potential Game ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Presymptomatic Stage ◽  
The Subject ◽  
Made In

The emergence of biomarkers in biologic fluids is considered an important milestone in the field of Alzheimer’s disease (AD) research. Biomarkers are widely considered critically important for the diagnosis and therapeutic intervention of the disease. It is believed that an early diagnosis of AD at a presymptomatic stage could provide the key for a successful intervention and treatment of AD. It is due to the reason that preventative and therapeutic strategies that are known to be AD stage-dependent can have a better chance of clinical success at a very early stage of the disease when critical neurons are not lost. To this end, current clinical trials are extensively being employed by taking advantage of different diagnostic biomarkers. While there has been notable progress in biomarkers for AD, the current research emphasis has been on exploring non-invasive biomarkers due to the advantages of cost-effectiveness, rapid diagnosis and significantly less medical procedural complexities that make these biomarkers potential game changer in AD diagnostics. Here, we present a bird eye view on the subject and discuss the progress made in important non-invasive biomarkers for AD.

Picture Recognition Errors in the Differential Diagnosis of Alzheimer’s Disease

2019 ◽  
Vol 30 (3) ◽  
pp. 157-168
Author(s):  
Helmut Hildebrandt ◽  
Jana Schill ◽  
Jana Bördgen ◽  
Andreas Kastrup ◽  
Paul Eling
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Clinical Diagnosis ◽  
Response Bias ◽  
Recognition Task ◽  
Discriminatory Power ◽  
False Alarms ◽  
Picture Recognition ◽  
Recognition Errors

Abstract. This article explores the possibility of differentiating between patients suffering from Alzheimer’s disease (AD) and patients with other kinds of dementia by focusing on false alarms (FAs) on a picture recognition task (PRT). In Study 1, we compared AD and non-AD patients on the PRT and found that FAs discriminate well between these groups. Study 2 served to improve the discriminatory power of the FA score on the picture recognition task by adding associated pairs. Here, too, the FA score differentiated well between AD and non-AD patients, though the discriminatory power did not improve. The findings suggest that AD patients show a liberal response bias. Taken together, these studies suggest that FAs in picture recognition are of major importance for the clinical diagnosis of AD.

Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review

2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affect Regulation ◽  
Current Evidence ◽  
Diagnostic Process ◽  
Neuropsychiatric Manifestation ◽  
The Brain ◽  
Control Functional

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

Leveraging Technology in Detection of Alzheimer’s Disease: A Systematic Review (Preprint)

2019 ◽  
Author(s):  
Clemens Kruse ◽  
Britney Larson ◽  
Reagan Wilkinson ◽  
Roger Samson ◽  
Taylor Castillo
Keyword(s):  
Magnetic Resonance Imaging ◽  
United States ◽  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The United States ◽  
Diagnostic Process ◽  
Resonance Imaging ◽  
Common Cause ◽  
Key Terms

BACKGROUND Incidence of AD continues to increase, making it the most common cause of dementia and the sixth-leading cause of death in the United States. 2018 numbers are expected to double by 2030. OBJECTIVE We examined the benefits of utilizing technology to identify and detect Alzheimer’s disease in the diagnostic process. METHODS We searched PubMed and CINAHL using key terms and filters to identify 30 articles for review. We analyzed these articles and reported them in accordance with the PRISMA guidelines. RESULTS We identified 11 technologies used in the detection of Alzheimer’s disease: 66% of which used some form of MIR. Functional, structural, and 7T magnetic resonance imaging were all used with structural being the most prevalent. CONCLUSIONS MRI is the best form of current technology being used in the detection of Alzheimer’s disease. MRI is a noninvasive approach that provides highly accurate results in the diagnostic process of Alzheimer’s disease.

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