MicroRNA-4422-5p as a Negative Regulator of Amyloidogenic Secretases: A Potential Biomarker for Alzheimer’s disease

Neuroscience ◽  
2021 ◽  
Author(s):  
Seyedeh Nazanin Hajjari ◽  
Saeed Sadigh-Eteghad ◽  
Dariush Shanehbandi ◽  
Shahram Teimourian ◽  
Ali Shahbazi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Negative Regulator ◽  
Potential Biomarker

scholarly journals Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aidan Kenny ◽  
Eva M. Jiménez-Mateos ◽  
María Ascensión Zea-Sevilla ◽  
Alberto Rábano ◽  
Pablo Gili-Manzanaro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unmet Need ◽  
Cost Effective ◽  
Specific Protein ◽  
Tear Fluid ◽  
Initiation Factor ◽  
Non Invasive ◽  
A Genome ◽  
Potential Biomarker

Abstract Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.

scholarly journals Exploratory human PET study of the effectiveness of 11C-ketoprofen methyl ester, a potential biomarker of neuroinflammatory processes in Alzheimer's disease

2016 ◽  
Vol 43 (7) ◽  
pp. 438-444 ◽  
Author(s):  
Akihito Ohnishi ◽  
Michio Senda ◽  
Tomohiko Yamane ◽  
Tomoko Mikami ◽  
Hiroyuki Nishida ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Methyl Ester ◽  
Potential Biomarker

Anticipatory and Reactive Grip Force Control in Patients with Alzheimer’s Disease: A Pilot Study

2021 ◽  
pp. 1-15
Author(s):  
Anna Gabriel ◽  
Carolin T. Lehner ◽  
Chiara Höhler ◽  
Thomas Schneider ◽  
Tessa P.T. Pfeiffer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Force Control ◽  
Grip Force ◽  
Object Manipulation ◽  
Step Test ◽  
Grip Force Control ◽  
Potential Biomarker ◽  
Neurological Conditions

Background: Alzheimer’s disease (AD) affects several cognitive functions and causes altered motor function. Fine motor deficits during object manipulation are evident in other neurological conditions, but have not been assessed in dementia patients yet. Objective: Investigate reactive and anticipatory grip force control in response to unexpected and expected load force perturbation in AD. Methods: Reactive and anticipatory grip force was investigated using a grip-device with force sensors. In this pilot study, fifteen AD patients and fourteen healthy controls performed a catching task. They held the device with one hand while a sandbag was dropped into an attached receptacle either by the experimenter or by the participant. Results: In contrast to studies of other neurological conditions, the majority of AD patients exerted lower static grip force levels than controls. Interestingly, patients who were slow in the Luria’s three-step test produced normal grip forces. The timing and magnitude of reactive grip force control were largely preserved in patients. In contrast, timing and extent of anticipatory grip forces were impaired in patients, although anticipatory control was generally preserved. These deficits were correlated with decreasing Mini-Mental State Examination scores. Apraxia scores, assessed by pantomime of tool-use, did not correlate with performance in the catching task. Conclusion: We interpreted the decreased grip force in AD in the context of loss of strength and lethargy, typical for patients with AD. The lower static grip force during object manipulation may emerge as a potential biomarker for early stages of AD, but more studies with larger sample sizes are necessary.

scholarly journals To Explore the Predictive Power of Visuomotor Network Dysfunctions in Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Justine Staal ◽  
Francesco Mattace-Raso ◽  
Hennie A. M. Daniels ◽  
Johannes van der Steen ◽  
Johan J. M. Pel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Support Vector Machine ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Predictive Power ◽  
Area Under The Curve ◽  
Classification Performance ◽  
Support Vector ◽  
Potential Biomarker

BackgroundResearch into Alzheimer’s disease has shifted toward the identification of minimally invasive and less time-consuming modalities to define preclinical stages of Alzheimer’s disease.MethodHere, we propose visuomotor network dysfunctions as a potential biomarker in AD and its prodromal stage, mild cognitive impairment with underlying the Alzheimer’s disease pathology. The functionality of this network was tested in terms of timing, accuracy, and speed with goal-directed eye-hand tasks. The predictive power was determined by comparing the classification performance of a zero-rule algorithm (baseline), a decision tree, a support vector machine, and a neural network using functional parameters to classify controls without cognitive disorders, mild cognitive impaired patients, and Alzheimer’s disease patients.ResultsFair to good classification was achieved between controls and patients, controls and mild cognitive impaired patients, and between controls and Alzheimer’s disease patients with the support vector machine (77–82% accuracy, 57–93% sensitivity, 63–90% specificity, 0.74–0.78 area under the curve). Classification between mild cognitive impaired patients and Alzheimer’s disease patients was poor, as no algorithm outperformed the baseline (63% accuracy, 0% sensitivity, 100% specificity, 0.50 area under the curve).Comparison with Existing Method(s)The classification performance found in the present study is comparable to that of the existing CSF and MRI biomarkers.ConclusionThe data suggest that visuomotor network dysfunctions have potential in biomarker research and the proposed eye-hand tasks could add to existing tests to form a clear definition of the preclinical phenotype of AD.

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

Lactobacillus probiotics improved the gut microbiota profile of a Drosophila melanogaster Alzheimer’s disease model and alleviated neurodegeneration in the eye

2020 ◽  
Vol 11 (1) ◽  
pp. 79-89 ◽  
Author(s):  
F.H.P. Tan ◽  
G. Liu ◽  
S.-Y.A. Lau ◽  
M.H. Jaafar ◽  
Y.-H. Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Gut Microbiota ◽  
Neurodegenerative Disorders ◽  
Dietary Intervention ◽  
Disease Model ◽  
Brain Health ◽  
Potential Biomarker ◽  
Microbiota Diversity

Alzheimer’s disease (AD) is a progressive disease and one of the most common forms of neurodegenerative disorders. Emerging evidence is supporting the use of various strategies that modulate gut microbiota to exert neurological and psychological changes. This includes the utilisation of probiotics as a natural and dietary intervention for brain health. Here, we showed the potential AD-reversal effects of Lactobacillus probiotics through feeding to our Drosophila melanogaster AD model. The administration of Lactobacillus strains was able to rescue the rough eye phenotype (REP) seen in AD-induced Drosophila, with a more prominent effect observed upon the administration of Lactobacillus plantarum DR7 (DR7). Furthermore, we analysed the gut microbiota of the AD-induced Drosophila and found elevated levels of Wolbachia. The administration of DR7 restored the gut microbiota diversity of AD-induced Drosophila with a significant reduction in Wolbachia’s relative abundance, accompanied by an increase of Stenotrophomonas and Acetobacter. Through functional predictive analyses, Wolbachia was predicted to be positively correlated with neurodegenerative disorders, such as Parkinson’s, Huntington’s and Alzheimer’s diseases, while Stenotrophomonas was negatively correlated with these neurodegenerative disorders. Altogether, our data exhibited DR7’s ability to ameliorate the AD effects in our AD-induced Drosophila. Thus, we propose that Wolbachia be used as a potential biomarker for AD.

scholarly journals Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Siddhartha Mondragón-Rodríguez ◽  
Humberto Salgado-Burgos ◽  
Fernando Peña-Ortega
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Connectivity ◽  
Aspartate Receptor ◽  
Potential Biomarker ◽  
Prodromal Ad ◽  
Brain Circuit ◽  
New Evidence ◽  
Ad Mouse Model

For more than five decades, the field of Alzheimer’s disease (AD) has focused on two main hypotheses positing amyloid-beta (Aβ) and Tau phosphorylation (pTau) as key pathogenic mediators. In line with these canonical hypotheses, several groups around the world have shown that the synaptotoxicity in AD depends mainly on the increase in pTau levels. Confronting this leading hypothesis, a few years ago, we reported that the increase in phosphorylation levels of dendritic Tau, at its microtubule domain (MD), acts as a neuroprotective mechanism that prevents N-methyl-D-aspartate receptor (NMDAr) overexcitation, which allowed us to propose that Tau protein phosphorylated near MD sites is involved in neuroprotection, rather than in neurodegeneration. Further supporting this alternative role of pTau, we have recently shown that early increases in pTau close to MD sites prevent hippocampal circuit overexcitation in a transgenic AD mouse model. Here, we will synthesize this new evidence that confronts the leading Tau-based AD hypothesis and discuss the role of pTau modulating neural circuits and network connectivity. Additionally, we will briefly address the role of brain circuit alterations as a potential biomarker for detecting the prodromal AD stage.

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