Current Alzheimer research最新文献

Introduction: Nowadays, the large increase in environmental pollutants has led to the occurrence and development of an increasing number of diseases. Studies have shown that exposure to environmental pollutants, such as methyl-4-hydroxybenzoate (MEP) may lead to Alzheimer's disease (AD). Therefore, the purpose of this study was to elucidate the complex effects and potential molecular mechanisms of environmental pollutants MEP on AD.

Methods: Through exhaustive exploration of databases, such as ChEMBL, STITCH, SwissTarget- Prediction, and Gene Expression Omnibus DataSets (GEO DataSets), we have identified a comprehensive list of 46 potential targets closely related to MEP and AD. After rigorous screening using the STRING platform and Cytoscape software, we narrowed the list to nine candidate targets and ultimately identified six hub targets using three proven machine learning methods (LASSO, RF, and SVM): CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5. The "clusterProfiler" R package was used to conduct GO and KEGG enrichment analysis. At the same time, we also constructed disease prediction models for core genes. At last, six hub targets were executed molecular docking.

Results: We derived 46 key target genes related to MEP and AD and conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. MEP might play a role in AD by affecting the pathways of neuroactive ligand-receptor interaction. Nine genes were screened as pivotal targets, followed by machine learning methods to identify six hub targets. Molecular docking analysis showed a good binding ability between MEP and CREBBP, BCL6, CXCR4, GRIN1, GOT2 and ITGA5. In addition, changes in the immune microenvironment revealed a significant impact of immune status on AD.

Discussions: This study revealed that MEP may induce AD through multiple mechanisms, such as oxidative stress, neurotoxicity, and immune regulation, and identified six core targets (CREBBP, BCL6, etc.) and found that they are related to changes in the immune microenvironment, such as T cells and B cells, providing new molecular targets for AD intervention.

Conclusion: Overall, CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5 have been identified as the crucial targets correlating with AD. Our findings provide a theoretical framework for understanding the complex molecular mechanisms underlying the effects of MEP on AD and provide insights for the development of prevention and treatment of AD caused by exposure to MEP.

Background: Alzheimer's disease is associated with dysfunction of the cholinergic system, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a promising therapeutic approach.

Objective: This study aimed to evaluate the neuroprotective effects and toxicity of essential oil (EO) and carlina oxide from Carthamus caeruleus in mice, assessing their potential for Alzheimer's disease treatment.

Methods: The chemical composition of the essential oil extracted from the roots of Carthamus caeruleus was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The main component, carlina oxide, was isolated via column chromatography. The inhibitory activities of AChE and BChE were evaluated in vitro for both the essential oil and carlina oxide. Additionally, in vivo, toxicity was assessed in laboratory mice.

Results: Chemical analysis identified carlina oxide (81.6%) as the major constituent, along with minor compounds such as 13-methoxycarlin oxide and hexadecanoic acid. Both the essential oil and its main component, carlina oxide, exhibited significant inhibitory activity against AChE and BChE, enzymes associated with Alzheimer's disease. The essential oil demonstrated promising IC₅₀ values, with stronger anti-BChE activity compared to the reference drug, galantamine. Toxicity tests in mice revealed no adverse effects at lower doses (0.2-0.5 g/kg). However, higher doses (1.0-2.0 g/kg) resulted in mild to significant toxicity, including weight loss and mortality.

Discussion: The essential oil and carlina oxide demonstrated potent BChE inhibition, particularly relevant in advanced Alzheimer's disease. While effective at low doses, signs of toxicity were observed at higher concentrations, highlighting the importance of dose optimization. These findings suggest that C. caeruleus may serve as a natural source of cholinesterase inhibitors, pending further in vivo studies and clinical validation.

Conclusion: Carthamus caeruleus essential oil and carlina oxide show promising inhibitory effects on AChE and BChE, suggesting their potential as neuroprotective agents. However, their toxicity at higher doses highlights the need for cautious use and further investigation.

Aims: This study seeks to examine the relationship between cerebrospinal fluid (CSF) biomarkers (Aβ1-42, Phospho-Tau181p, Total-Tau) and brain volumetric changes measured by Brain Shift Integral (BSI) in Alzheimer's disease (AD) spectrum. We explore the potential of BSI as a complementary, non-invasive tool for early diagnosis and progression monitoring of AD.

Background: AD is a neurodegenerative disorder marked by amyloid plaques and tau tangles, leading to cognitive decline. CSF biomarkers are key indicators of AD pathology, but their integration with imaging metrics like BSI could enhance early diagnosis. BSI quantifies brain volume changes via MRI, offering valuable insights into neurodegeneration across the AD spectrum.

Objectives: The current study explores the use of BSI and CSF biomarkers for the early detection of Alzheimer's disease.

Methods: This study utilized data from the ADNI database, including CSF biomarkers (Aβ1-42, t-tau, ptau181) and BSI measurements from baseline and month 24 visits. Spearman correlations were performed to assess associations between biomarkers and brain volumetric changes. Linear regression models were used to examine the predictive value of biomarkers on BSI, controlling for potential confounders.

Results: A total of 239 participants were included in the study, comprising 94 cognitively normal (CN) individuals, 104 with mild cognitive impairment (MCI), and 41 with AD. Significant negative correlations were observed between Aβ1-42 and both BBSI and VBSI in MCI at baseline (p=0.013) and 24 months (p=0.018), as well as between Aβ1-42 and VBSI in CN at baseline (p=0.039) and 24 months (p=0.033). In MCI, p-tau181 was positively correlated with BBSI (p=0.013) and VBSI (p=0.030) at baseline and with BBSI at 24 months (p=0.013). Linear regression analysis confirmed that Aβ1-42 and p-tau181 significantly predicted BSI measures in MCI (R²=0.141-0.173, p<0.05), while Aβ1-42 was a significant predictor of VBSI in CN (R2=0.156-0.166, p<0.01). No significant associations were found in AD.

Discussion: This study underscores the role of CSF biomarkers-particularly Aβ1-42 and p-tau181-in detecting early brain atrophy across the Alzheimer's disease spectrum, with limited utility in advanced stages. The findings highlight the importance of early intervention and support the integration of CSF biomarkers and BSI as diagnostic tools for monitoring disease progression and staging.

Conclusion: The application of the BSI is pivotal for monitoring brain volume alterations and their association with CSF biomarkers.

Alzheimer's disease (AD) and vascular dementia (VD) are the leading causes of dementia, presenting a significant challenge in differential diagnosis. While their clinical presentations can overlap, their underlying pathologies are distinct. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles, leading to progressive neurodegeneration. VD, on the other hand, arises from cerebrovascular insults that disrupt blood flow to the brain, causing neuronal injury and cognitive decline. Despite distinct etiologies, AD and VD share common risk factors such as hypertension, diabetes, and hyperlipidemia. Recent research suggests a potential role for oral microbiota in both diseases, warranting further investigation. The diagnostic dilemma lies in the significant overlap of symptoms including memory loss, executive dysfunction, and personality changes. The absence of definitive biomarkers and limitations of current neuroimaging techniques necessitate a multi-modal approach integrating clinical history, cognitive assessment, and neuroimaging findings. Promising avenues for improved diagnosis include the exploration of novel biomarkers like inflammatory markers, MMPs, and circulating microRNAs. Additionally, advanced neuroimaging techniques hold promise in differentiating AD and VD by revealing characteristic cerebrovascular disease patterns and brain atrophy specific to each condition. By elucidating the complexities underlying AD and VD, we can refine diagnostic accuracy and optimize treatment strategies for this ever-growing patient population. Future research efforts should focus on identifying disease-specific biomarkers and developing more effective neuroimaging methods to achieve a definitive diagnosis and guide the development of targeted therapies.

Alzheimer's disease (AD) has been ranked as the most common cause of dementia worldwide, which makes it a major cause of public health concern. The development of AD has been linked to a combination of factors, among which lifestyle-related factors can be targeted to minimize the risk of AD. A balanced diet acts as a source of all essential nutrients that can facilitate the functioning of the brain, promote cognitive longevity, safeguard against neurodegeneration, and, accordingly, reduce the risk of AD. Despite the availability of conclusive evidence highlighting the role of nutrition in the prevention of AD, a range of concerns have been identified that limit dietary adherence and public health efforts. This calls for the need to adopt a multipronged approach, including interventions targeting policy-level changes, the education sector, improvement in the food systems, and behavioural modifications to encourage long-term adherence to diets that are healthy for the brain. In conclusion, diet plays a crucial role in Alzheimer's disease, and there arises the need to incorporate food items that are healthy for the brain to maintain cognitive health and reduce the overall risk. The available data suggests that food items rich in antioxidants, omega-3 fatty acids, and B vitamins are associated with a lower risk of developing Alzheimer's disease.

Lecanemab, a therapeutic antibody designed to target amyloid-beta (Aβ) clearance, has recently been approved by the FDA and introduced in multiple countries, representing a significant milestone in advancing Alzheimer's disease (AD) treatment. However, its limited clinical efficacy underscores the need for further investigation of disease pathogenesis. Emerging evidence suggests that glucose and lipid metabolism dysfunction plays a critical role in AD, with metabolic changes emerging as one of the most significantly altered pathways in the early stage of pathology. These findings highlight the therapeutic potential of targeting metabolic regulation as a strategy to address AD.

Introduction: Alzheimer's Disease (AD) is the most prevalent progressive neurodegenerative disorder, leading to significant cognitive decline and dementia. Oxytocin (OXT), a peptide hormone synthesized in the hypothalamus, has emerged as a critical player in cognitive functioning. Notably, alterations in OXT levels have been reported in individuals with Alzheimer's disease.

Methods: This systematic review aims to synthesize existing literature from databases such as PubMed, Scopus, and Web of Science, focusing on the therapeutic potential of OXT in AD treatment. Two independent individuals conducted the screening procedure for all articles.

Results: Our screening revealed that studies investigating OXT therapy primarily involve animal models. These studies consistently demonstrate that, OXT administration mitigates various memory deficits in animal models of AD. These improvements are linked to mechanisms such as reduced microglial-driven inflammation and decreased amyloid-beta (Aβ) deposition, but changes in plaque load do not always correspond directly to cognitive improvement.

Discussion: While these findings are promising and oxytocin could be a potential therapeutic candidate for AD, the evidence is limited to animal studies. There is a lack of robust human data, making it difficult to draw firm conclusions about oxytocin's efficacy in people with AD. Ongoing and future clinical trials will be crucial to determine whether these preclinical benefits translate to humans.

Conclusion: Despite the limited number of studies examining the effects of OXT on AD and the inherent challenges in conducting such research, the available evidence from animal studies suggests promising results. These findings can serve as a valuable foundation for future human and complementary studies aimed at exploring oxytocin's therapeutic potential in treating AD.

Background: Prolonged or repeated psychological stress triggers dental and orthodontic diseases via inflammatory pathways and oxidative stress. This review aims to elucidate the role of inflammation, gut microbiota, stress, and cognition, exploring their impact on the development of therapeutics to enhance oral health.

Objective: The primary aim pertinent to this systematic review is to elucidate the significant implications of cognition and stress in dental and orthodontic health. Specifically, the review aims to (1) investigate the association between emotional stress and the incidence or progression of periodontal disease; (2) explore the impact of physiological and emotional stress on cellular and molecular inflammatory responses in orthodontics; (3) examine the influence of gut-mediated psychophysiological factors on emotional changes in mental health and cognition with a focus on periodontics and orthodontics; and (4) investigate the potential of gut microbiota alterations to influence oral and cognitive/mental health, including the impact of probiotic supplementation and dietary interventions.

Methods: A systematic review was conducted without comprehensive meta-analysis, focusing on literature from 1960 to 2024. Databases searched included PubMed, Embase, ReleMed, National Library of Medicine (NLM), Scopus, and Google Scholar. Keywords used were "cognition," "emotional stress," "gut microbiota," "orthodontics," "prosthetics," "pathophysiology," and "mental health." Studies were selected based on relevance, publication date, access to full texts, and adherence to PRISMA guidelines. The review integrated findings on the impact of emotional stress on periodontal disease and orthodontic health through pathophysiological implications.

Results: Age-related neurodegeneration causes Alzheimer's disease and severe dementia that subsequently promotes poor oral health. The review identified a complex interplay between emotional stress and periodontal disease. While a direct association remains to be conclusively proven, several studies highlight the influence of stress on the severity and incidence of periodontal disease through inflammatory and immunological pathways. Stress manifests in various ways, such as increased masticatory muscle tone, changes in eating behavior, and the initiation of bruxism, all of which can affect dental health. Physiological stress induces an inflammatory response to orthodontic tooth movement, impacting orthodontic treatment outcomes. Furthermore, the review elucidates the role of gut-mediated psychophysiological factors in emotional changes, influencing periodontal and orthodontic health. Emerging evidence suggests that gut microbiota alterations can significantly impact oral and cognitive health through systemic inflammation and neuroimmune mechanisms.

Conclusion: This review highlights the significant impa

Aim: This study aims to investigate the molecular mechanisms underlying Alzheimer's disease (AD) by analyzing differentially expressed miRNAs and their target proteins to identify key regulatory networks and therapeutic targets.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder with multifaceted regulatory mechanisms involving differentially expressed miRNAs. Recent studies suggest that understanding the target proteins of these miRNAs may reveal crucial insights into AD pathology.

Objective: The objective of this study was to investigate the role of differentially expressed miRNAs in Alzheimer's disease (AD) by identifying their target proteins and exploring the associated regulatory networks. This includes uncovering key hub proteins and their involvement in critical biological pathways linked to AD progression. Additionally, the study aims to identify transcription factors regulating these proteins and evaluate potential therapeutic compounds targeting these molecular players. By integrating these findings, the research seeks to provide a deeper understanding of AD pathogenesis and pave the way for novel therapeutic strategies to mitigate its progression.

Methods and materials: Differentially expressed miRNAs were collected from reviews, with target proteins identified using MiRDB, STRING, and Cytoscape. Promoter and transcription factor (TF) analyses were performed using Enrichr, and potential therapeutic compounds targeting hub proteins were explored via DrugBank.

Results: This study identifies key hub proteins, including TNF, PTEN, KRAS, ESR1, H3-3B, COL25A1, COL19A1, COL13A1, COL27A1, COL5A3, CCND1, FGF2, SMAD2, and PXDN, exploring their roles in AD progression. GO and KEGG pathway analyses revealed that hub proteins, including TNF, PTEN, KRAS, and ESR1, are involved in essential biological processes related to neural differentiation and signaling. Cytocluster analysis identified clusters with significant associations with AD, indicating complex interaction networks among these proteins.

Discussion: Potential therapeutic agents, including TNF inhibitors, estrogen receptor agonists, and KRAS inhibitors, were identified. Promoter and TF analysis further highlighted regulatory factors in AD pathways.

Conclusion: This study emphasizes crucial AD-related proteins and pathways, providing insights for future therapeutic targeting of gene expression to mitigate AD progression.