Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer

Bello-Medina, Paola C.; González-Franco, Diego A.; Vargas‐Rodríguez, Isaac; Dı́az-Cintra, Sofı́a

doi:10.1016/j.nrl.2019.06.002

Cited by 13 publications

(7 citation statements)

References 81 publications

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“…The pathogenesis of AD is highly complicated and involves multiple pathophysiological processes, including β-amyloid protein deposition, 15 phosphorylation of tau, 16 chronic inflammation, 17 neurotrophic disorder, 18 and oxidative stress, 19 among others. The combination of multiple factors leads to the occurrence of AD.…”

Section: Discussionmentioning

confidence: 99%

Serum miR-128 Serves as a Potential Diagnostic Biomarker for Alzheimer’s Disease

Zhang¹,

Han²,

Xu³

et al. 2021

NDT

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Background Although numerous microRNAs (miRNAs) have been discovered to participate in the progression of Alzheimer’s disease (AD), they are still difficult to apply in clinical work. Thus, the identification of novel miRNAs and clarification of their clinical significance are importing for improving the diagnosis and treatment of AD. The purpose of this study was to analyze the expression of miR-128 and its diagnostic value in patients with AD. Patients and Methods In this study, 117 AD patients and 106 controls were enrolled, and the demographic data, biochemical parameters and serum miR-128 levels were collected. These data were then used to build a logistic regression model, and receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic value of miR-128. The relationships between miR-128 and inflammatory factors (IL-1β/TNF-α) were also analyzed from clinical serum data. Results Our study found that miR-128 was significantly upregulated in the serum samples of AD patients compared with controls, and that this upregulation was negatively correlated with Mini-Mental State Examination (MMSE) scores ( r = −0.687, P < 0.01). ROC curve showed that the area under the curve of miR-128 was 0.831. Logistic regression analyses showed that glycosylated hemoglobin (HbA1c) levels, low-density lipoprotein (LDL) levels, MMSE scores and serum miR-128 levels were statistically significant ( P < 0.01), and the ROC curve of the combined detection of these variables was 0.906. The serum miR-128 levels in AD patients were positively correlated with the serum IL-1β ( r =0.798, P <0.01) and serum TNF-α levels ( r =0.733, P <0.01). Conclusion Serum miR-128 is a candidate diagnostic biomarker in AD patients who achieved good diagnostic performance when used alone or in combination with other factors and may have the potential to be a novel therapeutic target for neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Serum miR-128 Serves as a Potential Diagnostic Biomarker for Alzheimer’s Disease

Zhang¹,

Han²,

Xu³

et al. 2021

NDT

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“…In this pre-clinical model, extracellular Aβ-peptide accumulation within the hippocampus appears by 6 months old, and changes in tau occur at 12–15 months old; with hyperphosphorylated tau aggregates detected also in the hippocampus ( Oddo et al, 2003 ). These changes are associated with cognitive impairment in several behavioral paradigms, such as elevated maze, object recognition memory, Morris water maze, and T-maze tasks ( Oddo et al, 2003 ; Chen et al, 2013 ; Cantanelli et al, 2014 ; Morin et al, 2016 ; Davis et al, 2017 ; Wei et al, 2017 ; Bello-Medina et al, 2019a ). Histopathological and cognitive alterations have been mainly reported in the symptomatic stage of AD, i.e., at 6–9 months old, while learning and memory deficit have not been observed in the pre-symptomatic stage (3–5 months old) ( Guzmán-Ramos et al, 2012 ; Cantanelli et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Spatial Memory and Gut Microbiota Alterations Are Already Present in Early Adulthood in a Pre-clinical Transgenic Model of Alzheimer’s Disease

et al. 2021

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The irreversible and progressive neurodegenerative Alzheimer’s disease (AD) is characterized by cognitive decline, extracellular β-amyloid peptide accumulation, and tau neurofibrillary tangles in the cortex and hippocampus. The triple-transgenic (3xTg) mouse model of AD presents memory impairment in several behavioral paradigms and histopathological alterations from 6 to 16 months old. Additionally, it seems that dysbiotic gut microbiota is present in both mouse models and patients of AD at the cognitive symptomatic stage. The present study aimed to assess spatial learning, memory retention, and gut microbiota alterations in an early adult stage of the 3xTg-AD mice as well as to explore its sexual dimorphism. We evaluated motor activity, novel-object localization training, and retention test as well as collected fecal samples to characterize relative abundance, alpha- and beta-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) analysis in gut microbiota in both female and male 3xTg-AD mice, and controls [non-transgenic mice (NoTg)], at 3 and 5 months old. We found spatial memory deficits in female and male 3xTg-AD but no alteration neither during training nor in motor activity. Importantly, already at 3 months old, we observed decreased relative abundances of Actinobacteria and TM7 in 3xTg-AD compared to NoTg mice, while the beta diversity of gut microbiota was different in female and male 3xTg-AD mice in comparison to NoTg. Our results suggest that gut microbiota modifications in 3xTg-AD mice anticipate and thus could be causally related to cognitive decline already at the early adult age of AD. We propose that microbiota alterations may be used as an early and non-invasive diagnostic biomarker of AD.

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“…It is a main challenge of mental health research (Tian et al, 2019), and is clinically characterized by cognitive dysfunction, neuronal injury, and synapse loss (Vanderstichele et al, 2019). Currently, there are approximately 50 million AD patients in the world (Bello-Medina et al, 2019). Although donepezil and memantine could delay AD symptom progression, side effects have been reported.…”

Section: Introductionmentioning

confidence: 99%

An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer’s Patients

Liu

Guo³

2020

Front. Pharmacol.

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Alzheimer's disease (AD) is a common neurodegenerative disease, mainly manifested by cognitive dysfunction. It seriously reduces the quality of life, and there is no ideal treatment strategy in clinical practice. Clinical studies on the treatment of AD with Ginkgo biloba L. leaf extract (EGb) have been reported since 1980s, and many clinical studies have been carried out during the following 30 years. However, the benefits of EGb on the treatment of AD are still controversial. In this review, we collected the clinical trial reports of EGb on cognitive function from Pubmed, Elsevier, Europe PMC, and other database since the 1980s. Through analysis and comparison, we consider that EGb may be able to improve the cognitive function in patients who suffered from mild dementia during long-term administration (more than 24 weeks) and appropriate dosage (240 mg per day). The main evidences and existing problems of the negative and positive experimental results were summarized.

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Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer

Cited by 13 publications

References 81 publications

Serum miR-128 Serves as a Potential Diagnostic Biomarker for Alzheimer’s Disease

Serum miR-128 Serves as a Potential Diagnostic Biomarker for Alzheimer’s Disease

Spatial Memory and Gut Microbiota Alterations Are Already Present in Early Adulthood in a Pre-clinical Transgenic Model of Alzheimer’s Disease

An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer’s Patients

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