scholarly journals A novel kit for early diagnosis of Alzheimer’s disease using a fluorescent nanoparticle imaging

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jun Sung Park ◽  
Sang Tae Kim ◽  
Sang Yun Kim ◽  
Min Gi Jo ◽  
Myeong Jun Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Control Group ◽  
Fluorescent Nanoparticles ◽  
Ht22 Cells ◽  
Expression Levels ◽  
Nanoparticle Imaging ◽  
Fluorescent Nanoparticle ◽  
Primary Focus

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease and chronic illness with long preclinical phases and a long clinical duration. Until recently, a lack of potential therapeutic agents against AD was the primary focus of research, which resulted in less effort directed towards developing useful diagnostic approaches. In this study, we developed a WO2002/088706 kit that is composed of fluorescent nanoparticles for the early detection of AD. We provided a fluorescent nanoparticle for detecting markers and a kit for the early diagnosis of AD. The kit consists of a probe molecule comprising an oligonucleotide capable of detecting one or more AD-specific microRNAs (miRNAs) and biomarkers related to AD. Through screening, we selected miR-106b, miR-146b, miR-181a, miR-200a, miR-34a, miR-124b, miR-153, miR-155, Aβ1-42 monomer (mAβ), Aβ1–42 oligomer (oAβ), UCHL1, NLRP3, Tau, STAT3, SORL1, Clusterin, APOE3, APOE4, Nogo-A, IL-13, and Visfatin to serve as AD- and inflammation-related markers. For detection of kit-binding properties, we checked the expression levels of amyloid beta (Aβ), tau protein, and inflammatory mediators in APP/PS/ApoE knockdown (KD) mice and a control group using co-localisation analysis conducted with a confocal microscope. Using a similar approach, we checked the expression levels of miRNAs in HT22 cells. Finally, we used the plasma from AD patients to confirm that our fluorescent nanoparticles and the WO2002/088706 kit will provide a possible early diagnosis to serve as an AD detector that can be further improved for future studies on targeting AD.

scholarly journals Neuroprotective Effects of OMO within the Hippocampus and Cortex in a D-Galactose and Aβ25–35-Induced Rat Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Shaodong Deng ◽  
Hongmei Lu ◽  
Honggang Chi ◽  
Ying Wang ◽  
Xiao Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Energy Metabolism ◽  
Dose Group ◽  
Control Group ◽  
High Dose ◽  
Antioxidant Enzyme Activities ◽  
Group Model ◽  
Dependent Manner ◽  
Expression Levels

Morinda officinalis F.C. How. (Rubiaceae) is a herbal medicine. It has been recorded that its oligosaccharides have neuroprotective properties. In order to understand the oligosaccharides extracted from Morinda officinalis (OMO), a systematic study was conducted to provide evidence that supports its use in neuroprotective therapies for Alzheimer’s disease (AD). AD rat models were prepared with D-galactose and Aβ25–35. The following groups were used in the present experiment: normal control group, sham-operated group, model group, Aricept group, OMO low-dose group, OMO medium-dose group, and OMO high-dose group. The effects on behavioral tests, antioxidant levels, energy metabolism, neurotransmitter levels, and AD-related proteins were detected with corresponding methodologies. AD rats administered with different doses of OMO all exhibited a significant (P<0.05) decrease in latency and an increase (P<0.05) in the ratio of swimming distance to total distance in a dose-dependent manner in the Morris water maze. There was a significant (P<0.05) increase in antioxidant enzyme activities (SOD, GSH-Px, and CAT), neurotransmitter levels (acetylcholine, γ-GABA, and NE and DA), energy metabolism (Na+/K+-ATPase), and relative synaptophysin (SYP) expression levels in AD rats administered with OMO. Furthermore, there was a significant (P<0.05) decrease in MDA levels and relative expression levels of APP, tau, and caspase-3 in AD rats with OMO. The present research suggests that OMO protects against D-galactose and Aβ25–35-induced neurodegeneration, which may provide a novel strategy for improving AD in clinic.

scholarly journals Neuroprotective Effects of Probiotic-Supplemented Diet on Cognitive Behavior of 3xTg-AD Mice

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Chenxi Tan ◽  
Yang Liu ◽  
Huiyi Zhang ◽  
Cihan Di ◽  
Dechao Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Western Blot ◽  
Water Maze ◽  
Intestinal Flora ◽  
Gene Sequencing ◽  
Learning Ability ◽  
Control Group ◽  
Expression Levels ◽  
Y Maze

Alzheimer’s disease (AD) is recognized as one of the most common types of senile dementia. AD patients first suffer memory loss for recent events (short-term memory impairment). As the disease progresses, they are deprived of self-awareness. This study aims to explore the effects of a probiotic-supplemented diet on the cognitive behaviors and pathological features of mouse models of Alzheimer’s disease (AD). Mice in the control group and the 3xTg-AD group were fed a regular diet and a probiotic-supplemented diet, respectively, for 20 weeks. Behavioral experiments like Morris’s water maze and Y maze were conducted. Then, feces of mice were collected for 16S sRNA gene sequencing for microorganisms. In the end, soluble and insoluble Aβ40 and Aβ42 in the hippocampus and cortex of mice in each group were quantitatively analyzed with a double-antibody Sandwich ELISA. The expression levels of tau protein and gliocyte in the hippocampus and cortex were detected using the Western Blot method. The result of the Morris water maze experiment indicated that, in the place navigation test, the mice in the 3xTg-AD group experienced a significant decline in the learning ability and a longer escape latency and in the space exploration test, the swimming time of mice in the 3xTg-AD group in the target quadrant decreased and after being treated with the probiotic diet, mice in the 3xTg-AD group had improved learning and memory ability. The result of Y maze showed that the probiotic diet can improve the spontaneous alternation accuracy of mice in the 3xTg-AD group. The result of 16s rRNA gene sequencing showed that, compared with mice in the WT group, those in the 3xTg-AD group experienced a change in the intestinal flora. The Western Blot result displayed a decreased expression level of tau (pS202) ( P < 0.05 ) and decreased expression levels of Iba-1 and GFAP ( P < 0.05 ). The result of the ELISA experiment showed decreased levels of soluble and insoluble Aβ40 and Aβ42 in 3xTg-AD mice ( P < 0.05 ). In conclusion, a probiotic diet can prevent and treat AD by improving the intestinal flora of 3xTg-AD.

Identifying signs and symptoms preceding the diagnosis of Alzheimer’s Disease: a retrospective medical record review

2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X696881
Author(s):  
Fidelia Bature ◽  
Dong Pang ◽  
Yannis Pappas ◽  
Barbara Guinn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Medical Record ◽  
Clinical Diagnosis ◽  
Signs And Symptoms ◽  
Medical Record Review ◽  
Control Group ◽  
Record Review ◽  
Retrospective Medical Record Review

BackgroundEarly diagnosis of Alzheimer’s disease (AD) is beneficial as interventions work well at this stage.AimThe study sought to identify patterns in signs and symptoms as reported by patients, 10 years preceding the clinical diagnosis of AD and suggest a predictive model for the early detection of the disease.MethodA retrospective medical record review and nested case-control design were carried out on the charts of 109 individuals (37 cases and 72 in the control group) in three GP surgeries in Milton Keynes and Luton, diagnosed between the year 2006–2016. Data extracted included the demographic and clinical data (signs and symptoms preceding the diagnosis of the disease). Logistic regression and correlation coefficient was used for analysis of variables to identify patterns.ResultsAuditory disturbances (tinnitus), a symptom that has not been reported in AD, could have a diagnostic value with 3.03 increased odds for associating with AD and a P-value of ≤0.05; the symptom was presented with a mean age of 14.5 years before the clinical diagnosis of the disease. There was a positive correlation between auditory disturbance and AD; episodic memory and AD; the female gender and AD all at 1% level (2tailed).ConclusionAuditory disturbance in the form of tinnitus has not been fully investigated in AD apart from auditory hallucinations and, as this symptom has been associated with other conditions. While further research is advocated in a large scale due to the insufficiency of the sample to initiate subgroup analysis, the result suggests that auditory disturbance could be a confounding factor to support future plans to improve the early diagnosis of AD.

scholarly journals Assessment the Changes of Cortical Thickness in Alzheimer’s Disease in MR Images Using Freesurfer Software

2021 ◽  
Author(s):  
Nasim Sattari ◽  
◽  
Fariborz Faeghi ◽  
Babak Shekarchi ◽  
Mohammad Hossein Heidari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Sensitivity And Specificity ◽  
Cortical Thickness ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Significant Difference ◽  
The Mean ◽  
The Brain

Purpose: In this study, the main goal was to determine the correlation between the thickness of cerebral cortex and the severity of cognitive disorder in Alzheimer's disease Materials and method: Twenty patients diagnosed with Alzheimer’s disease with mean age of 72.95 year(14 women and 6 men) and Ten Cognitively normal (CN) subjects with mean age of 70.50 year( 7 women and 3 men) were included to the study. Of the AD patient and CN subjects, 70% were female and 30% were male. All individual underwent 1.5 T MRI. The MR scanning protocol included 3D MPRAGE (3D-T1W) sequence. All images were analyzed using Freesurfer v5.3 and then calculated the brain cortical thickness in 7 cortex( Inferior temporal, Middle temporal, Superior temporal, parahippocamp, parstriangularis, rostralmiddle frontal, Superior frontal). Result: The Analysis of covariance (ANCOVA) was conducted to compare the means of each region between the patient whilst control group. There was a significant difference in mean of cortical thickness in all regions. In all cases the mean of cortical thickness in CN subjects were greater than AD patients. However, the mean of Parstriangularis left hand in CN subjects was not significantly greater than the one in AD patients. The receiver operating characteristic system (ROC) was designed to evaluate the predictive power of the patient and the healthy person. We have selected a thousand cut-off points from 1.5 to 3.5mm for cortical thickness. When the cut-off points were interval (2.276878, 2.299680) millimeter in left hemisphere, the Youden’s index was maximized. The sensitivity and specificity in this case were 80%. Also when the cut-off points were within the range (2.263278, 2.282278) mm in right hemisphere, the sensitivity and specificity were 90% and 80%, respectively. Conclusion: This study demonstrates the importance of quantify the cortical thickness changes in early diagnosis of Alzheimer’s disease. In addition, examining the pattern of changes and the quantifying the reduction in the thickness of the cortex is an important tool for displaying the local and global atrophy of the brain. Also, this pattern can be used as an alternative marker for the diagnosis of dementia. Finally, to the best of our knowledge, our study is the first one to report finding on the range of cortical thickness that would help clinician to have better differential diagnose and also in this study have checked the possibility of early diagnosis of the disease.

scholarly journals Unearthing of Key Genes Driving the Pathogenesis of Alzheimer’s Disease via Bioinformatics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingxing Zhao ◽  
Hongmei Yao ◽  
Xinyi Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Cortex ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Machine Learning Algorithms ◽  
Functional Enrichment ◽  
Control Group ◽  
Hub Genes ◽  
Expression Levels

Alzheimer’s disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P &lt; 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P &lt; 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.

Effect of Bee Venom on an Experimental Cellular Model of Alzheimer’s Disease

2020 ◽  
Vol 48 (08) ◽  
pp. 1803-1819
Author(s):  
Yong Ho Ku ◽  
Jae Hui Kang ◽  
Hyun Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Bee Venom ◽  
Control Group ◽  
Cellular Model ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is a neurodegenerative disease and is characterized by the deposition of the [Formula: see text]-Amyloid peptide ([Formula: see text]A), which causes the inflammation of neurons. Bee venom (BV) elicits a strong anti-inflammatory response, and therefore we conducted an in vitro experiment to study the efficacy of BV in an AD cellular model. To mimic AD, the U87MG cell line was incubated for 168 hours with 2.5 [Formula: see text]M [Formula: see text]A. Changes were confirmed by microscopy, and peptides were measured under stain-free conditions using homo-tomography. Sulforhodamine B analysis was performed to analyze the cell viability. Real-Time quantitative polymerase chain reaction (qPCR) analysis was conducted to analyze mRNA expression levels of pro-inflammatory cytokines (NF-[Formula: see text]B, COX-2, TNF-[Formula: see text], IL-1), and Western blot was performed to measure the Caspase-3 protein levels. BV showed no cytotoxicity at concentrations below 10 [Formula: see text]g/mL. The NF-[Formula: see text]B mRNA levels were not significantly different between the BV group and the control group. The amount of [Formula: see text]A accumulation in the BV group decreased significantly. The mRNA expression levels of COX-2, TNF-[Formula: see text], and IL-1 were significantly reduced using 10 [Formula: see text]g/mL of BV compared to those in the control group. Additionally, Caspase-3 levels were also reduced compared to those of the control group when BV was used at a concentration of 10 [Formula: see text]g/mL. BV could inhibit apoptosis and inflammatory responses in an AD cellular model. In addition, it prevented cell accumulation of [Formula: see text]A, an important pathogenic mechanism in AD.

Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cell Damage ◽  
Control Group ◽  
Red Cell ◽  
Oxygen Release ◽  
Regulatory Pathways ◽  
Β Amyloid ◽  
2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

A Transfer Learning Approach for Early Diagnosis of Alzheimer’s Disease on MRI Images

Neuroscience ◽  
2021 ◽  
Author(s):  
Atif Mehmood ◽  
Shuyuan yang ◽  
Zhixi feng ◽  
Min wang ◽  
AL Smadi Ahmad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Transfer Learning ◽  
Learning Approach
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