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.

scholarly journals Isovitexin modulates autophagy in Alzheimer’s disease via miR-107 signalling

2020 ◽  
Vol 11 (1) ◽  
pp. 391-401
Author(s):  
Jiang Cheng ◽  
Guowei Wang ◽  
Na Zhang ◽  
Fang Li ◽  
Lina Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
The Elderly ◽  
Tnf Α ◽  
Autophagic Process ◽  
Molecular Signals ◽  
Ad Mouse Model ◽  
Mtor Signalling

AbstractBackground:Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.Methods:Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.Results:The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.Conclusion:This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.

scholarly journals Cerebrospinal Fluid α-Synuclein Predicts Neurodegeneration and Clinical Progression in Prodromal Alzheimer's Disease

2020 ◽  
Author(s):  
Jie-Qiong Li ◽  
Yan-Lin Bi ◽  
Xue-Ning Shen ◽  
Hui-Fu Wang ◽  
Wei Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Characteristic Curve ◽  
Longitudinal Change ◽  
Clinical Progression ◽  
Chinese Han ◽  
Predictive Values ◽  
Potential Biomarker ◽  
Prodromal Ad

Abstract BackgroundAccumulating reports suggest that α-synuclein is involved in Alzheimer disease (AD) pathogenesis. Cerebrospinal fluid (CSF) α-synuclein could be a potential biomarker of AD. We sought to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD. MethodsAssociations were investigated between CSF α-synuclein and other AD biomarkers at baseline in prodromal AD stage Chinese elders. The predictive values of CSF α-synuclein in longitudinal change in clinical outcomes and conversion risk of prodromal AD stage subjects were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in Alzheimer's disease Neuroimaging Initiative (ADNI) database.ResultsAmong individuals in prodromal AD stage, we detected that CSF α-synuclein levels correlated with AD-specific biomarkers CSF total tau and phosphorylated tau levels in 651 Chinese Han participants (training set). These positive correlations were replicated in ADNI database (validation set). Using a longitudinal cohort from ADNI, CSF α-synuclein concentrations increased with disease severity. CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” system (A+T+) vs controls (A-T-) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates CSF α-synuclein is a potentially useful, early biomarker for AD.

scholarly journals DNA Methylation: A Promising Approach in Management of Alzheimer’s Disease and Other Neurodegenerative Disorders

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 90
Author(s):  
Gagandeep Kaur ◽  
Suraj Singh S. Rathod ◽  
Mohammed M. Ghoneim ◽  
Sultan Alshehri ◽  
Javed Ahmad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Neurodegenerative Diseases ◽  
Epigenetic Modification ◽  
Research Area ◽  
Potential Biomarker ◽  
Novel Biomarkers ◽  
Different Populations

DNA methylation, in the mammalian genome, is an epigenetic modification that involves the transfer of a methyl group on the C5 position of cytosine to derive 5-methylcytosine. The role of DNA methylation in the development of the nervous system and the progression of neurodegenerative diseases such as Alzheimer’s disease has been an interesting research area. Furthermore, mutations altering DNA methylation affect neurodevelopmental functions and may cause the progression of several neurodegenerative diseases. Epigenetic modifications in neurodegenerative diseases are widely studied in different populations to uncover the plausible mechanisms contributing to the development and progression of the disease and detect novel biomarkers for early prognosis and future pharmacotherapeutic targets. In this manuscript, we summarize the association of DNA methylation with the pathogenesis of the most common neurodegenerative diseases, such as, Alzheimer’s disease, Parkinson’s disease, Huntington diseases, and amyotrophic lateral sclerosis, and discuss the potential of DNA methylation as a potential biomarker and therapeutic tool for neurogenerative diseases.

The Role of Methylated Circulating Nucleic Acids as a Potential Biomarker in Alzheimer’s Disease

2018 ◽  
Vol 56 (4) ◽  
pp. 2440-2449 ◽  
Author(s):  
Ming-Chyi Pai ◽  
Yu-Min Kuo ◽  
I-Fang Wang ◽  
Po-Min Chiang ◽  
Kuen-Jer Tsai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nucleic Acids ◽  
Circulating Nucleic Acids ◽  
Potential Biomarker

The role of N-methyl-D-aspartate receptor in Alzheimer's disease

2014 ◽  
Vol 339 (1-2) ◽  
pp. 123-129 ◽  
Author(s):  
Junsi Zhang ◽  
Yanna Li ◽  
Jing Xu ◽  
Zhou Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Aspartate Receptor

scholarly journals Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alberto Lleó ◽  
Henrik Zetterberg ◽  
Jordi Pegueroles ◽  
Thomas K. Karikari ◽  
María Carmona-Iragui ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Single Molecule ◽  
Area Under The Curve ◽  
Imaging Biomarkers ◽  
Potential Biomarker ◽  
Prodromal Ad ◽  
Asymptomatic Individuals ◽  
The Relationship

AbstractPlasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73–0.87] and 0.92 [95% CI 0.89–0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.

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