Current Alzheimer research最新文献

{"title":"Predictive Value of Complete Blood Count Parameters for Alzheimer's Disease in Relation to Periodontal Status.","authors":"Kubra Karaduran, Ahmet Aydogdu, Ozlem Gelisin, Sadiye Gunpinar","doi":"10.2174/0115672050388220250511174043","DOIUrl":"https://doi.org/10.2174/0115672050388220250511174043","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Given the role of inflammation in the development of both Alzheimer's disease (AD) and periodontal disease, it is plausible that periodontal disease may influence the progression of AD. Complete blood count (CBC) parameters may also serve as predictive indicators for this condition. This study investigated the predictive value of CBC parameters on the progression of AD in patients with periodontal disease.</p><p><strong>Methods: </strong>Data from a prospective cohort study (n=90) with 6-month follow-up was analyzed. AD was assessed based on the Clinical Dementia Rating Scale. Records of C-reactive Protein (CRP) levels and CBC parameters measured within the 6 months preceding the participation date were evaluated. Cognitive assessments at the initial and 6th-month follow-up were performed using the Standardized Mini-Mental Test (SMMT). All patients underwent clinical periodontal examination.</p><p><strong>Results: </strong>The difference in SMMT score change (ΔSMMT) and platelet distribution width (PDW) value between groups with and without periodontitis was statistically notable (p<0.05). The presence of periodontitis was found to be significantly associated with age, ΔSMMT, and PDW values using the multivariate logistic regression model (p<0.05). Furthermore, having Stage II and Stage III AD, periodontitis, age factor, and mean platelet volume (MPV) value had a notable impact on ΔSMMT (p<0.05).</p><p><strong>Conclusion: </strong>PDW and MPV levels may have a predictive significance in clarifying the association between periodontitis and AD progression.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Serum Lipid Traits and Cognitive Function in Middle-aged and Elderly Adults: A Longitudinal Study.","authors":"Chuning Luo, Qin Li, Ran Gao, Yijun Zhang, Yijie Wang, Fengyi Huang, Quanmei Li, Xite Zheng, Xiaorui Zhang, Wanqi Liu, Fen Liu","doi":"10.2174/0115672050370810250430112549","DOIUrl":"10.2174/0115672050370810250430112549","url":null,"abstract":"<p><strong>Background: </strong>It is debatable whether demographic factors alter the relationship between serum lipid traits and cognitive function. Few data have examined the effects of non-traditional lipid metrics on the lipid-cognition relationship. We aim to test the generality of relationships between lipid traits and cognitive function in Chinese adults.</p><p><strong>Methods: </strong>Data from 5,959 participants were obtained from the China Health and Retirement Longitudinal Study (2011-2020). The cognitive function was assessed via the Mini-Mental State Examination. Effects of traditional lipid metrics (Total Cholesterol, TC, Triglycerides, TG, Low-Density Lipoprotein, LDL, High-Density Lipoprotein, HDL) and non-traditional lipid metrics (TC/HDL, LDL/HDL) were analyzed. We employed mixed-effect models, Group-Based Trajectory Models (GBTM), and logistic regression to examine the associations between baseline serum lipid traits and cognitive function.</p><p><strong>Results: </strong>As continuous variables, higher TG levels were correlated with higher cognitive scores (P=0.036), and similar patterns were found in TC/HDL (P < 0.01) and LDL/HDL (P < 0.01). In contrast, higher HDL levels were associated with lower cognitive scores. Similar trends were observed when lipid traits were analyzed as categorical quartiles, and grouped by gender and age. Non-traditional lipid metrics (LDL/HDL, TC/HDL) had higher contributions to the variation of cognitive scores than traditional lipid metrics (TC, TG, LDL, HDL).</p><p><strong>Conclusion: </strong>Our study provided evidence for the generality of a significant association between traditional/non-traditional lipid metrics and cognitive function in middle-aged and elderly adults. The factors that vary with genders and age groups do not appear to significantly alter the lipid-cognition relationship.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of Nutrition in Supporting Brain Health and Reducing the Risk of Alzheimer's Disease.","authors":"Saurabh RamBihariLal Shrivastava, Prateek Sudhakar Bobhate","doi":"10.2174/0115672050397848250425060101","DOIUrl":"https://doi.org/10.2174/0115672050397848250425060101","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Default Mode Network Connectivity in Mild Cognitive Impairment: Insights from Resting-State fMRI Studies.","authors":"Danqi Zhang, Jinhuan Yue, Hanbin Niu, Zeyi Wei, Dong-Hong Huang, Peng Wang, Xiaoling Li, Yuhui Zhao, Qinhong Zhang","doi":"10.2174/0115672050352061250328055829","DOIUrl":"10.2174/0115672050352061250328055829","url":null,"abstract":"<p><p>Mild Cognitive Impairment (MCI) is marked by a measurable decline in cognitive function that exceeds typical age-related changes but does not yet qualify as dementia. The brain's Default Mode Network (DMN) remains active during rest and plays a crucial role in introspective processes, such as memory retrieval and self-referential thinking. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive neuroimaging technique that measures spontaneous fluctuations in blood oxygenation, providing insights into functional connectivity within brain networks. Investigating the DMN using rs-fMRI in individuals with MCI allows researchers to identify early neural changes associated with cognitive decline, which may serve as biomarkers for the early detection of Alzheimer's disease or related dementias. The rs-fMRI technique has been widely used in MCI research to explore the underlying neurobiological mechanisms of cognitive impairment. This study aims to synthesize findings from rs-fMRI studies focusing on alterations in DMN connectivity in MCI populations. This analysis deepens our understanding of the early-stage neural disruptions in MCI and holds significant implications for developing early diagnostic tools and interventions aimed at delaying the progression to dementia.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"83-91"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Relationships Between Neurodegenerative Diseases and Cancer Types: A Computational Approach.","authors":"Claudia Cava, Isabella Castiglioni","doi":"10.2174/0115672050389561250429112631","DOIUrl":"10.2174/0115672050389561250429112631","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies have shown a correlation between neurodegenerative diseases and cancers. However, the biological processes for these diseases are not completely known, and the genetic factors for their onset are not defined.</p><p><strong>Materials and methods: </strong>This study reports the genetic relationships of different neurodegenerative diseases, such as Multiple Sclerosis (MS), Alzheimer's Disease (AD), and Parkinson's disease (PD) and cancer types (squamous cell lung carcinoma, esophageal adenocarcinoma, and colorectal cancer), with other human traits, based on cross-trait Linkage Disequilibrium Score regression (LDSC). We then applied a clumping approach to select candidate genes for each disease, and via an miRNA analysis, we identified miRNAs that could regulate those genes.</p><p><strong>Results: </strong>LDSC revealed an inverse association of human traits with neurodegenerative diseases and cancer. Indeed, the cancer types studied were positively correlated with \"Body Mass Index (BMI),\" while AD, PD, and MS showed a negative correlation. miR-1-3p, miR-34a-5p, and miR-27a-3p were revealed as common biomarkers among the different pathological conditions.</p><p><strong>Conclusion: </strong>The present study suggests novel genetic associations between neurological diseases, cancer types and new targets to explain the genetic sharing between the diseases.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"232-246"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Framework for an Integrative Theory of Alzheimer's Disease.","authors":"Dmitry V Zaretsky, Maria V Zaretskaia","doi":"10.2174/0115672050381553250425062803","DOIUrl":"10.2174/0115672050381553250425062803","url":null,"abstract":"<p><p>The manuscript describes how the framework of the integrative hypothesis of Alzheimer's disease (AD) can be deciphered using existing experimental and clinical data. First, the analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies indicate a correlation between AD diagnosis and heightened cellular uptake of beta-amyloid. Since beta-amyloid must be taken up by cells to become toxic, its uptake rate correlates with neurodegeneration. Also, aggregation seeds cannot form extracellularly due to low beta-amyloid levels in interstitial fluid but can develop inside lysosomes. Consequently, the density of extracellular aggregates correlates positively with cellular amyloid uptake rate. The model, which ties both beta-amyloid cytotoxicity and aggregation to cellular uptake, accurately predicts AD diagnosis patterns in the population. Second, beta-amyloid enters cells through endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage and explains intracellular ion disturbances (including calcium overload) after exposure to extracellular beta-amyloid. The permeabilization is caused by channels formed in lysosomal membranes by some amyloid fragments produced by proteolysis of full-length beta-amyloid. Some membrane channels are large enough to leak cathepsins to the cytoplasm, causing necrosis or apoptosis. Also, local spikes of calcium cytosolic concentration due to calcium leakage from lysosomes can activate calpains, contributing to cell death. In surviving cells, accumulation of damaged lysosomes results in autophagy failure and slow mitochondrial recycling, promoting the production of reactive oxygen species and further cell damage. In this framework, AD's etiology is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization and the appearance of activated proteases in the cytoplasm. The correlation between AD diagnosis and the density of amyloid aggregates occurs because both amyloid cytotoxicity and extracellular aggregate formation stem from cellular amyloid uptake. To reflect key processes, we call this framework the Amyloid Degradation Toxicity Hypothesis of Alzheimer's Disease. It explains various phenomena and paradoxes associated with AD pathobiology across molecular, cellular, and biomarker levels. The hypothesis also highlights the limitations of current AD biomarkers and suggests new diagnostic and prognostic tools based on disease pathogenesis. Additionally, the framework identifies potential pharmacological targets for preventing disease progression.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"179-204"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Footprint of <i>CHASERR</i> as a Potential Culprit in Alzheimer's Disease Patients: An <i>In-Silico</i>-Experimental Study.","authors":"Zahra Khosroabadi, Anoosha Niazmand, Seyed Reza Mousavi, Neda Hosseini, Nastaran Bagheri, Ahmad Chitsaz, Mansoor Salehi","doi":"10.2174/0115672050381537250422075255","DOIUrl":"10.2174/0115672050381537250422075255","url":null,"abstract":"<p><strong>Objectives: </strong>Dementia has become a major global cause of death, posing significant health and economic challenges. Alzheimer's disease (AD) is the most common type of dementia. Recent studies have shown that long noncoding RNAs (lncRNAs) play a role in AD development. In this context, the current study conducted a comprehensive meta-analysis of high-throughput Gene Expression Omnibus (GEO) datasets to identify significant lncRNAs that could play a crucial role in the pathogenesis of AD.</p><p><strong>Methods: </strong>Three microarray expression profiles of human subjects diagnosed with AD and corresponding healthy controls were obtained from the GEO database. Afterward, the expression profiles from the chosen microarray datasets were combined. A network of differentially expressed genes (DEGs) was visualized, identifying key hub genes. Subsequently, the two significant lncRNAs, identified as <i>LINC01003</i> and <i>CHASERR</i>, were chosen based on the number of interactions between hubs and lncRNAs. Blood samples were collected from AD patients as well as from healthy control individuals. Ultimately, the expression levels of <i>CHASERR</i> and <i>LINC01003</i> were quantitatively assessed in the blood samples of 50 AD patients and 50 healthy controls using the quantitative Real-Time PCR (q-PCR) technique.</p><p><strong>Results: </strong>Experimental validation showed that <i>CHASERR</i> was differentially expressed in Alzheimer's disease (AD) patients compared to the control group. In contrast, LINC01003 revealed no significant difference between the AD patients and the control group.</p><p><strong>Conclusion: </strong>This study thoroughly examined the molecular landscape of AD, identifying key differentially expressed genes and highlighting candidate <i>CHASERR</i> as a potential molecular biomarker for AD patients.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"205-218"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Novel Mitochondrial Dysfunction-Related Alzheimer's Disease Diagnostic Model Using Bioinformatics and Machine Learning.","authors":"Kuo Zhang, Kai Yang, Gongchang Yu, Bin Shi","doi":"10.2174/0115672050353736241218054012","DOIUrl":"10.2174/0115672050353736241218054012","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) represents the most common neurodegenerative disorder, characterized by progressive cognitive decline and memory loss. Despite the recognition of mitochondrial dysfunction as a critical factor in the pathogenesis of AD, the specific molecular mechanisms remain largely undefined.</p><p><strong>Methods: </strong>This study aimed to identify novel biomarkers and therapeutic strategies associated with mitochondrial dysfunction in AD by employing bioinformatics combined with machine learning methodologies. We performed Weighted Gene Co-expression Network Analysis (WGCNA) utilizing gene expression data from the NCBI Gene Expression Omnibus (GEO) database and isolated mitochondria-related genes through the MitoCarta3.0 database. By intersecting WGCNA-derived module genes with identified mitochondrial genes, we compiled a list of 60 mitochondrial dysfunction- related genes (MRGs) significantly enriched in pathways pertinent to mitochondrial function, such as the citrate cycle and oxidative phosphorylation.</p><p><strong>Results: </strong>Employing machine learning techniques, including random forest and LASSO, along with the CytoHubba algorithm, we identified key genes with strong diagnostic potential, such as ACO2, CS, MRPS27, SDHA, SLC25A20, and SYNJ2BP, verified through ROC analysis. Furthermore, an interaction network involving miRNA-MRGs-transcription factors and a protein-drug interaction network revealed potential therapeutic compounds such as Congo red and kynurenic acid that target MRGs.</p><p><strong>Conclusion: </strong>These findings delineate the intricate role of mitochondrial dysfunction in AD and highlight promising avenues for further exploration of biomarkers and therapeutic interventions in this devastating disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"19-37"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Modulation in Alzheimer's Disease: Central Players in Neuroinflammation and Pathogenesis.","authors":"Md Sadique Hussain, Yumna Khan, Rabab Fatima, Mudasir Maqbool, Prasanna Srinivasan Ramalingam, Mohammad Gayoor Khan, Ajay Singh Bisht","doi":"10.2174/0115672050364292250113063513","DOIUrl":"10.2174/0115672050364292250113063513","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder of cognition with clinical features and anatomical hallmarks of amyloid-β plaques and/or neurofibrillary tangles. New studies revealed that microglia, the native immune cells in the brain, are crucial in the development of AD. The present review aims at outlining various roles of microglia in AD especially targeting their role in neuroinflammation. These indicate that microglial dysfunction contributes to AD pathology by affecting both amyloid-β phagocytosis and tau hyperphosphorylation. Other investigative molecular perpetrators, including TREM2, also influence the microglial relevance to amyloid and tau, as well as the overall disease phase. The functional microglia can protect neurons, while the dysfunctional one has the capability of derailing neuronal potentials and aggravating neurodegeneration. We have also discussed therapeutic strategies that start with targeting microglia to reduce neuroinflammation and reinstate balance. However, certain problems, including the side effects of microglial modulation, cost constraint, and accessibility, are areas of concern. In this review, the author presents the current state of knowledge on the potential of microglia-targeted treatments, their risks, and benefits. Thus, this article emphasizes the importance of the expansion of research to decipher the exact manipulation of microglia in AD with the goal of applying these findings given therapeutic approaches.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"56-82"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Regulation as a Potential Therapeutic Approach for Alzheimer's Disease.","authors":"Jinmiao Zhong, Jiaxin Sun, Bing Zhou","doi":"10.2174/0115672050379410250421065857","DOIUrl":"10.2174/0115672050379410250421065857","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"174-178"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}