جستجوی مقالات مرتبط با کلیدواژه « Alzheimer disease » در نشریات گروه « پزشکی »

Mesenchymal stem cell (MSC) transplantation represents a promising approach for treating Alzheimer’s disease (AD). These stem cells, however, have a short lifespan following transplantation into recipient animals. Selenium nanoparticles, due to their size, aid in drug delivery for brain disorders. This study investigated the therapeutic effect of MSCs and polyvinyl alcohol (PVA)-coated selenium nanoparticles (SeNPs) in a rat model of AD.

An Alzheimer-like phenotype was induced through intracerebroventricular (ICV) administration of streptozotocin (STZ).  Rats were assigned to five groups: control, Alz (STZ; 3 mg/kg, 10 μl, ICV), Alz+stem cell (ICV transplantation), Alz+SeNP (0.4 mg/kg, orally), and Alz+stem cell+SeNPs. The ICV administration of STZ mimicked some aspects of AD in the Alz groups. SeNPs were administrated for 30 days following STZ administration. The novel object recognition (NOR) and passive avoidance learning (PAL) tests were used to evaluate cognition and memory. Oxidative stress biomarkers and brain-derived neurotrophic factor (BDNF) were assessed by biochemical analysis, ELISA kits, and Congo red staining, respectively. 

The combined therapy of PVA-coated SeNPs and MSC transplantation was more effective in enhancing memory reacquisition compared to either SeNPs or MSCs alone. The use of stem cells in conjunction with PVA-coated SeNPs significantly boosted anti-oxidant capacity.

The results suggest that the joint treatment with PVA-coated SeNPs and MSCs offers considerable neuroprotection against AD in animal models.

 According to the cholinergic hypothesis for Alzheimer’s disease, potentiation of cholinergic neurotransmission is one of the best strategies for combating dementia.

 A new series of benzamide derivatives bearing 1,3,4-thiadiazole nucleus were synthesized and subsequently, their anticholinesterase activity was evaluated. Molecular docking was carried out to explore the likely binding mode and interactions.

 Fortunately, some of the tested compounds exhibited more activity than donepezil as a reference drug (IC50 = 0.6 ± 0.05 µM). Some of the evaluated derivatives displayed potency in the nanomolar range. Compound 7e with fluorine atom on the meta position of the phenyl ring was the most active compound in this series (IC50 = 1.82 ± 0.6 nM).

 The 1,3,4-thiadiazole derivatives that were synthesized and tested in the current manuscript demonstrated remarkable anticholinesterase activity. Therefore, these compounds could be suggested as potential anti-Alzheimer agents.

Cognitive disorders, characterized by transient stages and potential Alzheimer's disease, are influenced by changes in iron deposits in the brain. These changes can lead to toxicity and neuron death. Quantitative susceptibility mapping is used to accurately represent these changes, allowing for a more accurate evaluation of the time window of each cognitive disorder stage and the need for targeted treatment. The Alzheimer's Disease Neuroimaging Initiative research database was used to download the data and eight healthy participants and twenty-one participants with cognitive disorders based on MMSE cognitive test scores in 5 groups of cognitively normal, Subjective Memory Concern , Early Mild Cognitive Impairment, Late Mild Cognitive Impairment and Alzheimer's disease were included in this study. Quantitative Susceptibility Mapping processing was performed using the SEPIA toolbox in MATLAB, and segmentation was performed using FSL software. Finally, statistical analyzes were performed using SPSS V26 software. Statistically significant changes were observed in the QSM values of the right thalamus (p-value = 0.043) in the LMCI group and the right hippocampal nucleus (p-value = 0.050) in the control group. After one year, the right hippocampal nucleus shows increased iron accumulation in healthy individuals, suggesting that the nucleus is susceptible to the highest rate of iron deposition in healthy individuals. Based on this result, the hypothesis that iron deposits are the cause of the unknown cause-and-effect relationship between iron deposits and Alzheimer's disease may be confirmed.

The apolipoprotein E (APOE) genotype has a heterogeneous distribution throughout the world. The present study aimed to characterize the APOE genotype (rs429358, rs7412) in healthy individuals compared with Alzheimer cases in Kerman, southeastern Iran, by two standard mutation scanning methods. 

In this case-control study, 90 Alzheimer patients as a case group and 90 healthy individuals as a control group were examined. APOE genotyping was carried out using high-resolution melting (HRM) analysis assay and multiplex tetra-primer amplification-refractory mutation system polymerase chain reaction (T-ARMS PCR) techniques.

In contrast to Multiplex T-ARMS PCR, HRM analysis was not efficient in rs7412 genotyping. The results of multiplex T-ARMS showed that ε2ε3 genotype (P=0.006, odd ratio [OR]=0.119) and ε2 allele (P=0.004, OR=0.129) were more prevalent in the control group compared with the case ones, whereas ε4 allele was associated with borderline risk of Alzheimer disease (P=0.099, OR=1.76). 

We concluded that Multiplex T-ARMS PCR could be considered as a better option than HRM analysis for APOE genotyping in terms of speed, accuracy, simplicity, and cheapness in large-scale use. Also, the present study revealed that ε2 ε3 genotype and ε2 allele are protective against Alzheimer whereas the ε4 allele cannot be strongly considered as Alzheimer genetic risk factor in Kerman, Iran. The results may help to choose a better technique for APOE genotyping.

Metformin, as an insulin sensitizer, is a familiar antidiabetic drug. Increasing evidence points to metformin’s protective effects against Alzheimer’s disease (AD). However, the mechanism is not well understood. The present study evaluated whether inhibiting AMPK and activating mTOR could stop metformin from improving memory in rats with streptozotocin (STZ) -induced Alzheimer’s disease. Twelve-week-old Wistar rats, were injected 3 mg/kg STZ intracerebroventricularly on days 1 and 3 to develop the animal model. Metformin was applied orally at 100 mg/kg (17 days). Forty-five min before the retrieval phase, dorsomorphin (DM; AMPK inhibitor, 2 M) and MHY (mTOR activator, 0.1 M) were administered. Morris Water Maze (MWM) and shuttle box were utilized to measure spatial and passive avoidance memory, respectively. Congo red staining was used to identify cortical amyloid deposition. The findings exhibited a considerable enhancement in spatial learning and memory in the metformin treatment group (P≤0.05). Injection of DM and MHY alone could not significantly change MWM and passive avoidance. Additionally, co-administration of DM and MHY increased escape latency (P≤0.001) and reduced the total time spent in the target quadrant (TTS) (P≤0.05) compared to the STZ+MET group during retrieval of MWM. Also, co-injection of DM and MHY increased step-through latency (STL) and decreased time spent in the dark compartment (TDC) compared to the STZ+MET group (P≤0.001). Metformin appears to have a therapeutic impact by activating AMPK and inactivating mTOR. As a result, it could be used as an Alzheimer’s treatment strategy.

Neurodegenerative diseases (NDDs) cause progressive neuronal loss, resulting in morbidity and mortality. Research is continued on treatment strategies that can tackle the disease's pathophysiology and cease its progression. Considering the anti-apoptotic and neuroprotective properties of apelin, we hypothesized that apelin-13 could be a therapeutic solution for Alzheimer's disease and similar NDDs. Therefore, we evaluated its effect on scopolamine-treated rats.

Male rats (n=40) were assigned to 5 groups of 8. No intervention was considered for the control group. The scopolamine group received stereotaxic surgery and was treated with 3 mg/kg scopolamine intraperitoneally. The treatment groups were treated with scopolamine plus intraventricular injection of apelin-13 (1.25, 2.5, and 5 µg) into the right lateral ventricles for 7 days. For evaluating the memory impairment, the passive avoidance reactions of the animals, except the control group, were assessed 24 hours following the last injection. Regarding histological analysis, Congo red staining of the hippocampal sections was done, and immunoblotting was used to determine apoptotic biochemical markers, including caspase 3, cytochrome C, and congophilic amyloid-beta plaques.

Apelin–13 alleviated scopolamine-related passive avoidance memory impairment and reduced the number of congophilic amyloid-beta plaques in the hippocampus (all P<0.001). It attenuated the decrease in the mean levels of hippocampal apoptotic proteins (caspase 3, cytochrome C) in animals treated with scopolamine (all P<0.05).

The neuroprotective effects of apelin-13 suggest its therapeutic effect on neurodegenerative disorders.

Alzheimer disease (AD), as the leading cause of dementia and cognitive decline, requires innovative drug solutions addressing its multifaceted nature. To combat this complex disease, researchers explored various strategies, such as antioxidant mechanisms, promoting non-amyloidogenic pathways in amyloid precursor protein (APP) processing, inhibiting amyloid beta formation and polymerization, metal chelation, and cholinesterase inhibition. These diverse approaches aim to enhance AD’s neuro-protecting, cognitive-enhancing, and mood-modulating potential. Traditional medicine and pharmacy use plant secondary metabolites to mitigate AD side effects. Monoterpenes and diterpenes, characterized by their low molecular weight, exhibit valuable biological properties and clinical applications. Recent research has focused on their anti-AD properties. This study comprehensively reviews monoterpenes’ and diterpenes’ potential effects and mechanisms in addressing AD pathology. Additionally, clinical studies in this field are scrutinized, shedding light on the promising role of these secondary metabolites in managing AD.

Emerging evidence has shown that the glucagon-like peptide-1 (GLP-1) agonist can be used to treat Alzheimer disease; however, knowledge of its neural targets is limited. To understand the neural substrates of GLP-1, we have done whole brain mapping for GLP-1 and its receptor (GLP-1R), in 30 human brains.

GLP-1 expression was studied by immuno-histochemistry and confirmed by the western blot method. The GLP-1R gene expression was studied by reverse transcription polymerase chain reaction.

GLP-1 expression was observed in most of the cortical areas (maximum in frontal, prefrontal and parietal cortex), diencephalon, and brainstem, but not in the cerebellum. Protein expression studies validated these results. The highest expression of GLP-1R was found in the frontal cortex. The orbitofrontal cortex and cerebellum had negligible expression. Hippocampus demonstrated a significant presence of GLP-1R but patchy immunoreactivity to GLP-1. GLP-1R presence in most of the human cortical regions and absence in the cerebellum is the major deviation from the animal brain. Sites that might be of interest in Alzheimer have been identified. GLP-1 demonstrated an age-related decline in most of the areas after the fifth decade. At 60 years, GLP-1 was not found in any of the cortical areas except in the prefrontal cortex; however, it was present in the sub-cortical areas.

Age-related profiling of GLP-1 in various brain areas has been analyzed, which can have an important bearing on understanding Alzheimer disease. This study provides a detailed description of GLP-1 and an brain mapping for the first time and may lead to novel treatment options targeting the GLP-1 receptors.

Recently, the role of sports training and medicinal plants in the expression of genes has been considered to prevent the progression of diseases. The purpose of this research was to investigate the role of weight training and oleander extract on interferon regulatory factor 8 (IRF8) and cathepsin S (CTSS) gene expression in the soleus muscle of Alzheimer's disease (AD) model mice.

Fifty-five male Wistar rats were randomly divided into 5 groups: healthy control group, AD control group, AD resistance training group, AD group with the supplement of Melilotus officinalis, and AD resistance training group + Melilotus officinalis supplement. Trimethyltin-induced AD was induced. In the resistance training protocol, a weight was attached to the tail of the rats, and they had to lift this weight on a ladder with 26 steps. Melilotus officinalis was injected intraperitoneally as a supplement for 6 weeks with a dose of 300 mmol/kg. Seventy-two hours after the last training session, the rats were anesthetized, and the hippocampal tissue was immediately extracted, frozen, and analyzed. A two-way analysis of variance was used to estimate the differences between groups in control and experimental AD mice.

There was a significant increase in the expression level of interferon-regulating factor 8 and cathepsin S genes in the AD group compared to the control group. The results of Bonferroni's post-hoc test showed that in the AD group + resistance training + Melilotus officinalis, a significant decrease was observed compared to the AD group (P≤0.05).

Resistance training and the Melilotus officinalis extract with antioxidant mechanisms can affect CTSS and IRF8 gene expression.

Family caregivers of patients with Alzheimer face many challenges when caring for them. The patients need not only the care of health professionals but also social support. Therefore, this study aimed to summarize the existing studies on social support for family caregivers of Alzheimer patients in a systematic review.

In this review, the search was done in domestic (Magiran, SID) and foreign (Web of Science, Scopus, ProQuest, PubMed) databases as well as Google Scholar from 1990 to August 2021, according to the PRISMA (Preferred Reporting Items for Systematic Reviews) statement. The Cochrane and STROBE checklists were used to evaluate the quality of the articles.

Out of 709 articles on social support in family caregivers of Alzheimer patients, 7 entered the final list. The number of family caregivers participating in these studies ranged from 81 to 648. The mean age of caregivers in all studies was over 50 years. The studies emphasized the importance of improving social support in family caregivers of Alzheimer patients. Most study studies were conducted in America, which included all the interventional studies in this systematic review. In most studies, social support’s role in reducing family caregivers’ problems and promoting their satisfaction was important. 

Creating social networks and encouraging the use of these supports will be very helpful in reducing the problems of family caregivers of Alzheimer patients. More attention to health literacy is likely useful as a revelation of the need for social support in family caregivers of Alzheimer patients and the government.

Functional Magnetic Resonance Imaging (fMRI) is a non-invasive neuroimaging tool, used in brain function research and is also a low-frequency signal, showing brain activation by means of Oxygen consumption.  One of the reliable methods in brain functional connectivity analysis is the correlation method. In correlation analysis, the relationship between two time-series has been investigated. In fMRI analysis, the Pearson correlation is used while there are other methods. This study aims to investigate the different correlation methods in functional connectivity analysis. In this analytical research, based on fMRI signals of Alzheimer’s Disease (AD) and healthy individuals from the ADNI database, brain functional networks were generated using correlation techniques, including Pearson, Kendall, and Spearman. Then, the global and nodal measures were calculated in the whole brain and in the most important resting-state network called Default Mode Network (DMN). The statistical analysis was performed using non-parametric permutation test.  Results show that although in nodal analysis, the performance of correlation methods was almost similar, in global features, the Spearman and Kendall were better in distinguishing AD subjects. Note that, nodal analysis reveals that the functional connectivity of the posterior areas in the brain was more damaged because of AD in comparison to frontal areas. Moreover, the functional connectivity of the dominant hemisphere was disrupted more.   Although the Pearson method has limitations in capturing non-linear relationships, it is the most prevalent method. To have a comprehensive analysis, investigating non-linear methods such as distance correlation is recommended.

endurance and resistance exercise and the consumption of hawthorn alone and in combination have an effect on Alzheimer's disease.This study was conducted with the aim of the effect of hawthorn consumption and exercise on the inflammatory indices of Alzheimer's rats by trimethyltin chloride (TMT).

rats were randomly divided into 9 healthy control and Alzheimer's groups with interventions (control, endurance training, resistance training, combined training, hawthorn, endurance training + hawthorn, resistance training + hawthorn, combined training + hawthorn). Then Alzheimer's disease developed. performed resistance , combined ,endurance exercises every week (12 weeks). Finally, blood was taken from the inferior vena and the inflammatory variables CRP, IL-6 ,TNF-α were measured by ELISA method. The Shapiro-Wilk test was used to check the normal distribution of the data, and the one-way analysis of variance (ANOVA) was used to check the mean difference between the groups (Tukey's test). P ​​<0.05 were considered statistically significant.

results showed that the induction of Alzheimer's disease induced by TMT caused a significant increase in the levels of TNF α, IL 6, CRP in the Alzheimer's control group compared to the healthy control. And 12 weeks of combined training with and without hawthorn had a significant decrease in the level of these variables compared to Alzheimer's control.

As a result, endurance and resistance sports along with the consumption of hawthorn lead to the reduction of some inflammatory factors in Alzheimer's rats.