Curr Alzheimer Res [JOURNAL]
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Retraction Notice: Optimized Turmeric Extract Reduces β-Amyloid and Phosphorylated Tau Protein Burden in Alzheimer's Transgenic Mice.
Shytle RD, Tan J, Bickford PC … +8 more , Rezaizadeh K, Hou L, Zeng J, Sanberg PR, Sanberg CD, Alberte RS, Fink RC, Roschek B
Curr Alzheimer Res · 2025 · PMID 40442971 · Full text
This article titled "Optimized Turmeric Extract Reduces β-Amyloid and Phosphorylated Tau Protein Burden in Alzheimer's Transgenic Mice," published in Volume 9, Issue 4, 2012 of Current Alzheimer Research (10.2174/1567205...
This article titled "Optimized Turmeric Extract Reduces β-Amyloid and Phosphorylated Tau Protein Burden in Alzheimer's Transgenic Mice," published in Volume 9, Issue 4, 2012 of Current Alzheimer Research (10.2174/156720512800492459 ) has been retracted by the publisher following a thorough investigation that revealed potential data manipulation in the manuscript. As a result, the integrity and validity of the data presented could not be confirmed. The retraction has been made in agreement with the Editor-in-Chief. Despite multiple attempts, the authors did not respond to correspondence regarding this matter. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Retraction can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
Evaluating the Therapeutic Effects of Oxytocin on Animal Model of Alzheimer's Disease: A Systematic Review.
Shafigh E, Sadeghi G, Jamaat NA … +3 more , Hassanpour F, Solhirad M, Karimi-Zandi L
Curr Alzheimer Res · 2025 · PMID 40417765 · Publisher ↗
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 hypothalamu...
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.
Environmental Enrichment and Metformin Combination Improves Cognitive Function through BDNF and HPA Axis in Chronically Stressed Rats.
Bhagya VR, Tilak K, Kanimozhi L … +1 more , Sushma R
Curr Alzheimer Res · 2025 · PMID 40415296 · Publisher ↗
INTRODUCTION: Chronic stress is a major global health issue linked to conditions such as anxiety, depression, and cognitive decline. In rodent studies, chronic immobilization stress (CIS) is commonly used to investigate...
INTRODUCTION: Chronic stress is a major global health issue linked to conditions such as anxiety, depression, and cognitive decline. In rodent studies, chronic immobilization stress (CIS) is commonly used to investigate the neuropsychological effects of prolonged stress, leading to behaviours such as anhedonia, anxiety, and depressive-like symptoms. An enriched environment (EE) provides physical, cognitive, and sensory stimulation, which promotes social interaction, supports brain development, and can enhance the effectiveness of pharmacological treatments, improving overall therapeutic outcomes. Metformin, commonly prescribed for type 2 diabetes, has antidiabetic effects and helps reduce oxidative stress, inflammation, and cell death in the brain, which may contribute to its neuroprotective properties. This study aims to evaluate the effectiveness of metformin, an enriched environment (EE), and its combination in alleviating anxiety and depression-like behaviours, memory impairments, and metabolic changes. MATERIALS AND METHODS: Rats were exposed to chronic immobilization stress (CIS) for 2 hours per day over a period of 10 days, followed by 14 days of treatment with metformin (200 mg/kg) and 6 hours of daily exposure to an enriched environment (EE). Behavioural tests, including the open field test (OFT), elevated plus maze (EPM), sucrose preference test (SPT), and novel object recognition test (NORT), were conducted. After completing the behavioural assessments, the animals were euthanized, and their plasma levels of corticosterone (CORT), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, triglycerides, and glucose were measured. Additionally, the concentration of brainderived neurotrophic factor (BDNF) in the hippocampus was analysed. RESULTS: Rats exposed to chronic immobilization stress (CIS) exhibited increased anxiety and depressive- like behaviours, as well as poor performance in the novel object recognition test (NORT). These behavioural changes were linked to elevated levels of plasma corticosterone (CORT), LDL, cholesterol, triglycerides, and glucose, along with decreased HDL levels and lower hippocampal BDNF. Treatment with metformin, an enriched environment (EE), or their combination alleviated these effects, improving exploratory behaviour, sucrose preference, and recognition memory and reducing anxiety-like behaviours. These benefits were accompanied by increased hippocampal BDNF expression, elevated plasma HDL, and reduced levels of CORT, LDL, cholesterol, triglycerides, and glucose. DISCUSSION: The combination of metformin and an enriched environment completely restored cognitive impairment and metabolic alterations in chronic stress conditions. Metformin's ability to improve energy metabolism and reduce oxidative stress could be further enhanced in an enriched environment, which promotes cognitive function and resilience to stress. CONCLUSION: Therefore, evidence suggests that EE can positively influence the outcomes of the neuroprotective effects of metformin and present promising therapeutic approaches for mitigating stress-induced behavioural and biochemical alterations.
IoMT Requirements, Integrated Diagnosis, and Future Trends for Multimodal Early Detection of Alzheimer's Disease.
Khosravi MM, Parsaei H
Curr Alzheimer Res · 2025 · PMID 40415295 · Publisher ↗
Abstract loading — click title to view on PubMed.
Predictive Value of Complete Blood Count Parameters for Alzheimer's Disease in Relation to Periodontal Status.
Karaduran K, Aydogdu A, Gelisin O … +1 more , Gunpinar S
Curr Alzheimer Res · 2025 · PMID 40396318 · Publisher ↗
INTRODUCTION/OBJECTIVE: 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 b...
INTRODUCTION/OBJECTIVE: 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. METHODS: 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. RESULTS AND DISCUSSION: 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). These findings may indicate that systemic inflammation as reflected by complete blood count parameters (such as PDW and MPV) may play a predictive role in cognitive decline in Alzheimer's disease patients with periodontitis. CONCLUSION: PDW and MPV levels may have a predictive significance in clarifying the association between periodontitis and AD progression.
Association Between Serum Lipid Traits and Cognitive Function in Middle-aged and Elderly Adults: A Longitudinal Study.
Luo C, Li Q, Gao R … +8 more , Zhang Y, Wang Y, Huang F, Li Q, Zheng X, Zhang X, Liu W, Liu F
Curr Alzheimer Res · 2025 · PMID 40377148 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. METHODS: 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. RESULTS: 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). DISCUSSION: Results of this study further supported the protective effect of TG and negative effect of HDL in elderly adults, though confounding factors like baseline cognitive heterogeneity warrant future investigation. Notably, non-traditional lipid ratios demonstrated stronger predictive value for cognitive variation than individual lipid metrics. CONCLUSION: 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.
Preface.
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Curr Alzheimer Res · 2025 · PMID 40353401 · Publisher ↗
Abstract loading — click title to view on PubMed.
The Framework for an Integrative Theory of Alzheimer's Disease.
Zaretsky DV, Zaretskaia MV
Curr Alzheimer Res · 2025 · PMID 40353400 · Publisher ↗
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-i...
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.
Exploring the Role of Nutrition in Supporting Brain Health and Reducing the Risk of Alzheimer's Disease.
Shrivastava SR, Bobhate PS
Curr Alzheimer Res · 2025 · PMID 40353399 · Publisher ↗
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 whi...
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.
Investigating the Relationships Between Neurodegenerative Diseases and Cancer Types: A Computational Approach.
Cava C, Castiglioni I
Curr Alzheimer Res · 2025 · PMID 40353398 · Publisher ↗
INTRODUCTION: 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 ons...
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: The present study suggests novel genetic associations between neurological diseases, cancer types and new targets to explain the genetic sharing between the diseases.
NRN1 may Modulate Tau Phosphorylation and Neuronal Apoptosis in AD the PIGU-CASP3 Axis.
Cheng W, Zhang J, Zhu H … +10 more , Wang Z, Li M, Wang J, Fu H, Zhang Y, Gao Y, Chen C, Yuan C, Zhu J, Sun J
Curr Alzheimer Res · 2025 · PMID 40296620 · Publisher ↗
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by hyperphosphorylation of tau protein to form neurofibrillary tangles (NFTs) and amyloid β (Aβ) deposition to form senile pl...
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by hyperphosphorylation of tau protein to form neurofibrillary tangles (NFTs) and amyloid β (Aβ) deposition to form senile plaques, and its specific regulatory mechanism remains incompletely understood. Neurotrophic factors (NTFs) play important roles in neuronal growth, differentiation, and survival, and are considered to have potential therapeutic effects in AD. OBJECTIVE: This study aimed to investigate the effects of NTFs on tau protein phosphorylation in AD and its underlying mechanisms. METHODS: A correlation analysis was conducted between neurotrophic factors and tau protein phosphorylation genes using bioinformatics analysis. The relationship between the candidate neurotrophic factor NRN1 and tau protein phosphorylation was validated . The effects of NRN1 on tau protein phosphorylation, neural process-related proteins, and apoptosis were explored . Subsequently, GO and KEGG pathway enrichment analyses and PPI network were utilized to identify potential functions and pathways, as well as pinpoint core regulatory factors. Finally, the mechanism by which NRN1 affects tau protein phosphorylation was explored through Western blot analysis. RESULTS: Bioinformatics analysis revealed a significant negative correlation between NRN1 and MAPT, a gene linked to tau protein phosphorylation. Western blot analysis indicated a decrease in NRN1 expression and an increase in p-tau levels in the hippocampus of AD mice. NRN1 significantly reduced the expression of p-tau in AD cell models and enhanced the expression of MAP2, a protein related to neural processes. Further, apoptosis analysis demonstrated that NRN1 significantly decreased the level of cleaved caspase-3 and elevated the Bcl-2/Bax ratio. Bioinformatics analysis and PPI network construction suggested PIGU and CASP3 to play pivotal roles in NRN1 regulation of tau protein phosphorylation. CONCLUSION: NRN1 may mitigate tau protein phosphorylation and neuronal apoptosis by modulating the PIGU-CASP3 pathway in AD. This finding offers novel insights into NRN1 as a potential target for the treatment of AD.
The Footprint of as a Potential Culprit in Alzheimer's Disease Patients: An -Experimental Study.
Khosroabadi Z, Niazmand A, Mousavi SR … +4 more , Hosseini N, Bagheri N, Chitsaz A, Salehi M
Curr Alzheimer Res · 2025 · PMID 40296619 · Publisher ↗
OBJECTIVES: 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 noncodin...
OBJECTIVES: 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. METHODS: 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 and , 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 and were quantitatively assessed in the blood samples of 50 AD patients and 50 healthy controls using the quantitative Real-Time PCR (q-PCR) technique. RESULTS: Experimental validation showed that 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. CONCLUSION: This study thoroughly examined the molecular landscape of AD, identifying key differentially expressed genes and highlighting candidate as a potential molecular biomarker for AD patients.
Social Isolation as a Risk Factor for Dementia: Insights from Animal Model Studies.
Araki W
Curr Alzheimer Res · 2025 · PMID 40296618 · Publisher ↗
Social isolation (SI) and loneliness (perceived social isolation) are considered as risk factors for developing dementia, including Alzheimer's disease (AD), in the elderly population. Intriguingly, recent reports have s...
Social isolation (SI) and loneliness (perceived social isolation) are considered as risk factors for developing dementia, including Alzheimer's disease (AD), in the elderly population. Intriguingly, recent reports have shown a significant association of loneliness with a higher amyloid- β (Aβ) burden, suggesting that SI is linked to the pathophysiology of AD. Numerous studies, using rodents or other animal models have revealed diverse biological effects of SI, including induction of oxidative stress and activation of neuroinflammation. Furthermore, using transgenic mouse models of AD, recent investigations have shown that SI affects AD pathology, particularly the deposition of Aβ and neuroinflammation. However, it remains unclarified, by which mechanisms SI confers a significant risk for AD. In this narrative mini-review, I overview published studies on the pathobiological effects of SI in rodent models and discuss the mechanisms by which SI exacerbates AD pathology. Clarification of this issue has significant implications for the design of strategies for preventing cognitive impairment and dementia in the elderly population.
Metabolic Regulation as a Potential Therapeutic Approach for Alzheimer's Disease.
Zhong J, Sun J, Zhou B
Curr Alzheimer Res · 2025 · PMID 40289967 · Publisher ↗
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...
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.
Unraveling the Intricacies: The Role of miRNAs in the Progression and Initiation of Alzheimer's Disease.
Amerizadeh F, Farzadifar E
Curr Alzheimer Res · 2025 · PMID 40277064 · Publisher ↗
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...
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 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.
Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.
Rodriguez-Casado A, Alvarez MI, Merino JJ … +2 more , Toledano-Díaz A, Toledano A
Curr Alzheimer Res · 2025 · PMID 40231540 · Publisher ↗
OBJECTIVE/BACKGROUND: Type 2 Diabetes Mellitus (T2D) and Alzheimer's disease (AD) are two diseases with a high prevalence today that share common pathophysiological mechanisms, suggesting a potential causal relationship...
OBJECTIVE/BACKGROUND: Type 2 Diabetes Mellitus (T2D) and Alzheimer's disease (AD) are two diseases with a high prevalence today that share common pathophysiological mechanisms, suggesting a potential causal relationship between them. AD is also known as Type 3 Diabetes Mellitus (T3D). A complete understanding of this complex issue (T2D-AD) is necessary to develop fully effective and easily applicable therapies that do not yet exist. A critical update on the subject is presented, delving into the pathophysiological implications and defining new research for promoting new therapeutic interventions. METHODS: Revision and critical analysis of the described and observed cellular and molecular common pathogenic T2D-AD mechanisms in human and model studies. RESULTS: Both diseases exhibit common genetic, epigenetic, biochemical and physiological characteristics. Pathogenic mechanisms such as peripheral inflammation, mitochondrial dysfunction, oxidative stress, insulin resistance, hyperglycemia, formation of advanced glycation end products, neuroinflammation, neuroglial dysfunctions, and deposition of aberrant misfolded proteins are commonly displayed in dysmetabolic diseases and AD. The T2D, AD and T2D-AD pathogenic courses present several close key contacts (or identities). The clinical course of T2D has different incidence in the neurodegenerative course of AD (from its onset to its aggravation). There are theoretical, practical and interpretative problems in studies on human and experimental models, as well as in the clinical and pathological interpretation of T2D-AD dementia, which are of great importance in the development of knowledge of this subject and the therapeutic application of its results. CONCLUSION: In recent years, there has been a great advance in the study of the relationships between T2D (and related dysmetabolic diseases) and AD. There is no doubt about their close relationship and/or the inclusion of AD as a metabolic disease (T3D). Joint therapies seem to be absolutely necessary. Key pathogenic processes (insulin resistance, genetic and epigenetic regulation, peripheral inflammation and neuroinflammation) must be investigated to develop new and effective therapies.
Influence of Inflammation, Gut Microbiota, and Stress on Cognition and Oral Health Therapies.
Liye A, Saichao Z, Zhang X … +3 more , Loktionova M, Gavrikov LK, Glazachev O
Curr Alzheimer Res · 2025 · PMID 40231539 · Publisher ↗
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, stre...
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 impact of physiological and emotional stress on periodontal and orthodontic health. Detailed exploration of cellular and molecular inflammatory responses provides insights into the pathophysiology of orthodontic diseases and their impact on oral health. Gut-brain-oral axis has significance in oral health, exploring how alterations in gut microbiota influence oral and cognitive health. It is essential to investigate the impact of probiotic supplementation and dietary modifications on gut microbiota composition, systemic inflammation, and their influence on both cognitive and oral health. Clinical trials assessing the effectiveness of anti-inflammatory treatments in reducing periodontal disease and cognitive decline could offer valuable insights. Integrating advanced microbiome analysis techniques and neuroimaging can help clarify the mechanisms linking gut health, systemic inflammation, and cognitive function. Exploring specific gut microbiota strains that regulate systemic inflammation and cognitive function may lead to targeted probiotic therapies, potentially alleviating neuroinflammation and enhancing cognitive performance. Additionally, understanding the role of oral probiotics in periodontal health and their effects on gut microbiota and systemic inflammation could contribute to the development of innovative treatment approaches. This knowledge can aid molecular biologists, dentists, and researchers in managing oral and gut health more effectively.
Altered Default Mode Network Connectivity in Mild Cognitive Impairment: Insights from Resting-State fMRI Studies.
Zhang D, Yue J, Niu H … +6 more , Wei Z, Huang DH, Wang P, Li X, Zhao Y, Zhang Q
Curr Alzheimer Res · 2025 · PMID 40231538 · Publisher ↗
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...
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.
Analysis of the Relationship Between NLRP3 and Alzheimer's Disease in Oligodendrocytes based on Bioinformatics and Experiments.
Li C, Chen Y, Yao Y … +3 more , Zhang Y, Tong S, Shang Y
Curr Alzheimer Res · 2025 · PMID 40207815 · Publisher ↗
AIMS: This study aims to explore the potential association between nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in oligodendrocytes and Alzheimer's disease (AD), utilizing a combination of bi...
AIMS: This study aims to explore the potential association between nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in oligodendrocytes and Alzheimer's disease (AD), utilizing a combination of bioinformatics analysis and molecular biology experiments to validate this relationship. METHODS: Public datasets related to AD were systematically retrieved and downloaded from the Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI). Subsequently, the SVA package was employed to merge the data and eliminate batch effects, allowing for the precise identification of differentially expressed genes (DEGs) between AD patients and healthy controls. Advanced machine learning techniques, including LASSO regression analysis, random forest algorithms, and support vector machines (SVM), were utilized to analyze further the DEGs associated with the NLRP3 inflammasome to determine the gene set most closely related to AD. The effectiveness and clinical value of the gene-based diagnostic model were comprehensively assessed through receiver operating characteristic (ROC) curve analysis, nomogram construction, and decision curve analysis (DCA). Immune infiltration analysis evaluated the extent of various immune cell infiltrations in the brain tissue of AD patients. Single-cell transcriptomics and experiments were conducted to verify the molecular expression of NLRP3 in oligodendrocytes within the AD model. RESULTS: A total of 11 significant DEGs were identified, with 4 genes showing downregulation and 7 genes exhibiting upregulation. All three algorithms-LASSO regression, random forest, and SVM-consistently identified PANX1, APP, P2RX7, MEFV, and NLRP3 as key genes closely associated with AD. ROC curve analysis, nomogram modeling, and DCA results demonstrated that the diagnostic model constructed based on these five genes exhibited high diagnostic accuracy and clinical applicability. Immune infiltration analysis revealed a significant correlation between key genes associated with AD and various immune cells, particularly CD8+ T cells, monocytes, activated NK cells, and neutrophils, suggesting that these cells may play important roles in the immunopathological process of AD. Single-cell transcriptomics indicated that the expression level of NLRP3 in oligodendrocytes was higher in the AD group compared to the control group (p < 0.05). Additionally, cell experiments using Reverse transcription quantitative PCR(RT-qPCR), immunofluorescence (IF), and Western blot (WB) analysis confirmed that the expression level of NLRP3 in oligodendrocytes was elevated in the AD model relative to the control group (p < 0.05). CONCLUSION: This study corroborates the high expression of NLRP3 in AD and its close relationship with the disease through integrated bioinformatics analysis and molecular biology experiments. Furthermore, the diagnostic model constructed based on the five key genes-PANX1, APP, P2RX7, MEFV, and NLRP3-not only provides a robust tool for early diagnosis of AD but also offers new insights for the development of treatment targets for AD.
User Experience in Virtual Reality (VR) Applications for Elderly People with Cognitive Impairment and Dementia: A Scoping Review.
Buele J, Aviles-Castillo F, Palacios-Navarro G
Curr Alzheimer Res · 2024 · PMID 40033596 · Publisher ↗
BACKGROUND: In recent years, Virtual Reality (VR) has emerged as a promising tool to improve the well-being and functional capabilities of older adults. Although VR applications have shown positive results, their impact...
BACKGROUND: In recent years, Virtual Reality (VR) has emerged as a promising tool to improve the well-being and functional capabilities of older adults. Although VR applications have shown positive results, their impact on user experience and therapeutic outcomes still needs to be evaluated. OBJECTIVE: This scoping review aims to analyze existing studies on VR use in older adults with neurodegenerative disorders, focusing on the factors that influence usability, satisfaction, and immersion, as well as the effects on emotional and cognitive well-being. MATERIALS AND METHODS: Empirical studies in English were included on VR applications applied to older adults with cognitive impairment without study design restrictions. The search was conducted in IEEE Xplore, PubMed, Scopus, and Web of Science, identifying a total of 650 initial results. After screening, 14 studies met the inclusion criteria. RESULTS: Immersive VR tends to generate a greater sense of presence, which contributes to improving emotional well-being and reducing neuropsychiatric symptoms, such as apathy and depression. However, its impact on cognitive functions, including memory and executive skills, varied depending on the level of immersion and participant characteristics. Despite these positive findings, significant heterogeneity was evident in study designs, measurement instruments, and user experience indicators. CONCLUSION: Virtual environments have great potential as a therapeutic tool for older adults, but their success depends on the personalization of applications and the adaptation of technology to the specific needs of this population. Future research should focus on developing standardized protocols, incorporating adaptive technologies such as artificial intelligence, and evaluating the longterm effects of VR to maximize its benefits and minimize its risks. This review was registered in Open Science Framework (OSF). REGISTRATION NUMBER: 10.17605/OSF.IO/PNU36.
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