Current Alzheimer research最新文献

{"title":"Proteomic Basis of Polypharmacological Cognitive Recovery in Down Syndrome and Alzheimer's Disease.","authors":"Handan Kulan","doi":"10.2174/0115672050471158260716112026","DOIUrl":"https://doi.org/10.2174/0115672050471158260716112026","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Down Syndrome (DS) is a genetic disorder caused by trisomy of human chromosome 21 and represents the most common genetic cause of intellectual disability. It is also associated with an increased risk of developing Alzheimer's Disease (AD). Although various pharmacological treatments have been shown to improve learning and memory in DS models, the underlying mechanisms of cognitive improvement remain poorly understood. This study aims to identify molecular signatures associated with pharmacological cognitive rescue across different brain regions using a machine learning-guided targeted proteomics approach.</p><p><strong>Methods: </strong>Gradient Boosting Tree (GBT)-based feature selection combined with Principal Component Analysis (PCA) was applied to identify reproducible proteomic signatures in cortical samples from memantine-treated mice and in hippocampal samples from RO4938581-treated mice.</p><p><strong>Results: </strong>GBT models achieved classification accuracies exceeding 80% across experimental groups, and PCA showed distinct group separation, with PC1 and PC2 accounting for more than 60% of the total variance. The consistently identified proteins across datasets include APP, RCAN1, S6/pS6, IL1B, BAX, TAU, AMPKA, BRAF, ERK, and ADARB1.</p><p><strong>Discussion: </strong>The identified proteins converge on interconnected networks linking synaptic signaling, metabolic regulation, and neuroinflammation, reflecting pathways involved in Excitation/İnhibition (E/I) imbalance and neurodegeneration. Their consistency across datasets implies that coordinated regulation of these networks, rather than isolated pathway effects, is associated with cognitive improvement. Specifically, the MAPK-ERK and AMPK-mTOR signaling pathways emerge as key integrative nodes connecting synaptic function, energy balance, and cellular stress responses. These results point to possible mechanistic overlap with Alzheimer's disease-related pathology and support a network-based, multi-target model of cognitive improvement in DS.</p><p><strong>Conclusion: </strong>These results demonstrate that different pharmacological treatments converge on shared protein signatures associated with cognitive improvement in DS. This convergence supports a network- based, multi-target therapeutic approach, in which modulation of key regulatory nodes rather than single targets may underlie effective treatment strategies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803761","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":"Audio‒Visual Gamma Stimulation for Alzheimer's Disease: Current Evidence and Future Directions.","authors":"Fateme Maghsoudlou, Ali Esteki","doi":"10.2174/0115672050478693260720114427","DOIUrl":"https://doi.org/10.2174/0115672050478693260720114427","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Alzheimer's Disease (AD) is characterized by progressive cognitive decline and disrupted neural oscillations. Recently, 40 Hz gamma stimulation has emerged as a potential non-invasive therapy. This review evaluates the safety, tolerability, and clinical outcomes of this intervention based on evidence from the past decade.</p><p><strong>Methods: </strong>A literature search was conducted across PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published during the last ten years. Registered and ongoing studies were also identified through ClinicalTrials.gov. Extracted data included stimulation modality, stimulation parameters, safety and tolerability outcomes, and reported effects on functional connectivity, brain atrophy, cognitive performance, and sleep-related measures.</p><p><strong>Results: </strong>Thirty studies were identified, comprising eight sensory-based 40-Hz gamma stimulation approaches, 12 40-Hz transcranial Alternating Current Stimulation (tACS) protocols, and 10 ongoing clinical trials. Among the 20 completed studies, 40-Hz gamma stimulation was reported to be safe and well-tolerated. The synthesized evidence from these completed trials suggests potential beneficial effects on functional connectivity, brain atrophy progression, cognitive outcomes, and sleep-related measures.</p><p><strong>Discussion: </strong>Gamma stimulation may represent a promising approach for modulating neural network activity and cognitive function in AD. Nevertheless, current evidence remains limited by small sample sizes, methodological heterogeneity, differences in stimulation protocols, and short follow-up periods. These factors limit the ability to draw definitive conclusions regarding therapeutic efficacy.</p><p><strong>Conclusion: </strong>40-Hz gamma stimulation is a feasible and generally well-tolerated non-invasive intervention with potential relevance for AD treatment. Further large-scale, randomized, and controlled studies are required to establish standardized stimulation protocols, determine long-term efficacy, and clarify its clinical utility.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148709201","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":"Depression and Risk of Alzheimer's Disease: A Mendelian Randomization Study.","authors":"Chongyang Liu, Bao-Peng Liu, Fang Pan, Anis Larbi, Tze Pin Ng, Yanxia Lu","doi":"10.2174/0115672050477354260714063740","DOIUrl":"https://doi.org/10.2174/0115672050477354260714063740","url":null,"abstract":"<p><strong>Introduction/background: </strong>Recent studies show that depression often occurs years before Alzheimer's disease onset in many older adults. However, it is unclear whether this link reflects a causal relationship.</p><p><strong>Materials and methods: </strong>Summary statistics from Genome-Wide Association Studies (GWAS) of depression and Alzheimer's disease were utilized. Data associated with broad depression included up to 407,746 Europeans, and data associated with major depression disorder included up to 480,359 Europeans; the corresponding Alzheimer's disease associations from consortia included up to 488,285 European participants in the UK Biobank. Two-sample Mendelian randomization analyses served as our primary approach, with additional three-sample analyses performed to validate the findings.</p><p><strong>Results: </strong>In the sample of 407,746 participants, genetically predicted levels of broad depression showed no significant association with Alzheimer's disease risk (odds ratio, 1.00007; p = 0.908). As for the sample of 480,359 participants associated with major depressive disorder, the result was consistent (odds ratio, 0.99918, p = 0.138) with findings from broad depression. Secondary analyses present consistent results with primary findings. Statistically significant bias from pleiotropy or genetic confounding was not detected in sensitivity analyses.</p><p><strong>Discussion: </strong>The study's findings do not support a causal role of depression in AD and are more consistent with depression reflecting early disease processes or shared mechanisms.</p><p><strong>Conclusion: </strong>This study's Mendelian randomization approach revealed no causal relationship between depression and Alzheimer's disease, consistent with depression reflecting early disease manifestations rather than a direct causal factor, and hinting at possible shared pathological processes in both conditions.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611665","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":"Cognitive Profiles in Early- and Late-Onset Alzheimer's Disease: The Role of Dementia Severity in Typical Amnestic Presentations Using the Addenbrooke's Cognitive Examination III.","authors":"Anna Barczak, Anna Krempa-Kowalewska, Maciej Golan","doi":"10.2174/0115672050489392260702044957","DOIUrl":"https://doi.org/10.2174/0115672050489392260702044957","url":null,"abstract":"<p><strong>Introduction: </strong>Early-Onset (EOAD) and Late-Onset Alzheimer's Disease (LOAD) are often described as presenting distinct cognitive phenotypes. However, reported differences are inconsistent and may reflect demographic and severity-related confounding rather than stable etiological distinctions.</p><p><strong>Materials and methods: </strong>A retrospective analysis was conducted in 776 patients with clinically diagnosed Alzheimer's disease (EOAD, n = 175; LOAD, n = 601). Cognitive performance was assessed using the Addenbrooke's Cognitive Examination III (ACE-III) and the Mini-Mental State Examination (MMSE). Dementia severity was staged using the Functional Assessment Staging Tool (FAST). Cognitive outcomes were analysed using age- and severity-adjusted ANCOVA models including a diagnosis × age interaction. Severity-stratified and domain-level analyses were also performed.</p><p><strong>Results: </strong>Unadjusted analyses revealed limited EOAD-LOAD differences in the Attention and Visuospatial domains, with small effect sizes. After adjustment for demographic variables and dementia severity, no cognitive measure reliably differentiated EOAD from LOAD. Cognitive performance showed similar cross-sectional patterns across groups and was primarily determined by dementia severity.</p><p><strong>Discussion: </strong>Small, stage-dependent differences observed at mild and moderate stages did not persist in more advanced dementia and did not indicate stable cognitive dissociation between EOAD and LOAD.</p><p><strong>Conclusions: </strong>After adjustment for demographic factors and dementia severity, EOAD and LOAD do not exhibit distinct cognitive profiles on ACE-III. Cognitive performance reflects disease stage rather than age at onset, supporting the use of ACE-III for staging cognitive impairment rather than for differentiating EOAD from LOAD in typical amnestic presentations.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611694","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":"Integrating Multi-Omics and Mendelian Randomization Reveals the Role of Epstein-Barr Virus Infection in Alzheimer's Disease and the Therapeutic Potential of Resveratrol.","authors":"Xu Wang, Jinjian Li, Zhen Wei, Chunshu Rong, Dexi Zhao, Yue Wang","doi":"10.2174/0115672050463115260708111634","DOIUrl":"https://doi.org/10.2174/0115672050463115260708111634","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The pathogenesis of Alzheimer's disease (AD) is complex, with immune system dysregulation playing a critical role. However, the specific molecular mechanisms linking peripheral immune responses to central pathologies in AD remain unclear. This study aims to systematically screen for reliable plasma biomarkers of AD by integrating transcriptomics, Mendelian randomization (MR) of plasma proteomics, and bioinformatics analyses, and to explore their potential pathogenic mechanisms and therapeutic drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Transcriptomic sequencing of plasma samples from three AD patients and three healthy controls was first performed to identify differentially expressed genes (DEGs) and perform functional enrichment analyses. The aim of this study is to provide a preliminary indication of gene expression changes based on real patient samples for subsequent MR and bioinformatics analyses, rather than serving as confirmatory evidence. Following this, two-sample MR was performed to explore the potential causal relationship between plasma proteins and AD in genetic prediction, and MR-positive results were intersected with transcriptome DEGs to identify highconfidence targets. After that, protein-protein interaction (PPI) analysis, functional enrichment (GO/KEGG), and transcription factor (TF) target network analysis were conducted. Based on the KEGG pathway analysis, the causal association between antibodies related to Epstein-Barr virus and AD in genetic prediction was further evaluated. In the end, the diagnostic power of core biomarkers was validated in the GEO dataset. Potential therapeutic drugs were screened in the CTD database, followed by verification through molecular docking and molecular dynamics simulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;Our transcriptomic enrichment analysis of DEGs indicates that AD is significantly correlated with viral infection and immune and inflammatory pathways. According to the results of MR analyses, 36 plasma proteins have a causal effect on AD in genetic prediction. Among these 36 targets, two pathways are identified as enriched: \"EBV Infection\" and \"Efferocytosis\". Seven core targets are CR2, ICAM1, TAPBP, TNFAIP3, THBS1, SCARF1, and SIRPG. Also, the concentration of antibodies against EBV EBNA-1 and VCA p18 was confirmed by MR analyses to be risk factors for AD. According to drug predictions, molecular docking, and molecular dynamics simulations, resveratrol can stabilize CR2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This study systematically identifies major plasma immune biomarkers associated with AD and proposes a mechanism by which EBV infection regulates plasma proteins CR2, TNFAIP3, and THBS1, which may affect AD risk. Resveratrol is thought to have preventive and protective effects, as predicted computationally.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study systematically identified key plasma markers associated with AD. Resveratrol is likely to becom","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611700","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":"Combining MRI-Derived Imaging Measures and Peripheral Proteomics to Improve the Mechanistic Understanding of Alzheimer's Disease Beyond Core Pathology: A Scoping Review.","authors":"Oceanna Yueran Li, Dabne Herrera Guerra, Mia Anthony, Karen Oh, Feng Vankee-Lin, Adam Turnbull","doi":"10.2174/0115672050472412260629113636","DOIUrl":"https://doi.org/10.2174/0115672050472412260629113636","url":null,"abstract":"<p><strong>Introduction/background: </strong>Alzheimer's Disease (AD) core pathology involves amyloidβ and ptau, leading to neurodegeneration (ATN model), yet individuals with comparable core pathology show considerable biological and clinical heterogeneity, motivating new models that consider non-specific processes and co-pathology. MRI and peripheral proteomics offer complementary, non-invasive approaches for capturing biological variation beyond core pathology, and many researchers have begun integrating them. However, no systematic overview of this literature exists. This scoping review evaluated studies combining MRI and peripheral plasma proteomics in AD within revised diagnostic frameworks, summarizing strengths and gaps.</p><p><strong>Materials and methods: </strong>Following PRISMA 2020 guidelines, PubMed, Embase, and Scopus were searched through June 14, 2023, yielding 3,185 records; 63 studies met the inclusion criteria. For each study, study design, participant characteristics, proteomic platforms, imaging modalities, statistical approaches, and significant associations between non-core-pathological proteins and MRIderived measures were extracted.</p><p><strong>Results: </strong>Across studies, methodological variability was high. Grey matter volume was the most commonly examined imaging metric, followed by cerebrovascular dysfunction, cortical thickness, white-matter and whole-brain volume, and connectivity measures. Overall, 127 non-core-pathology proteins, mostly related to inflammation/immune function, were associated with MRI metrics, though only three appeared in five or more studies. Roughly half of the studies incorporated core AD biomarkers.</p><p><strong>Discussion: </strong>This scoping review of 63 studies demonstrates that integrating peripheral proteomics with MRI is an increasingly common approach in AD research, with GFAP, CRP, and IL-6 as the most frequently reported proteins, and grey matter volume and vascular dysfunction as the most commonly examined imaging phenotypes. However, effect sizes are generally modest, findings are heterogeneous, and many studies lack core AD biomarkers, highlighting the need for greater methodological consensus and more mechanistic, multimodal, and longitudinal research.</p><p><strong>Conclusion: </strong>Integrating MRI and peripheral proteomics is increasingly common in AD research, but consensus on analytic and imaging approaches is limited. Heterogeneity in proteomic platforms and statistical methods constrains comparability; most associations are modest, and observational designs limit causal inference. Future work should emphasize methodological harmonization, reproducibility, multivariate and machine-learning approaches, and randomized trials to test mechanistic pathways.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521679","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":"Cardiovascular Comorbidities with Alzheimer's Disease: A Systematic Review and Meta-analysis.","authors":"Juliano Flávio Rubatino Rodrigues, Lívia Peregrino Rodrigues, Franciany Cunha Peregrino Rodrigues, Luiza Lorenz Cavalcante, Spencer Luiz Marques Payão, Almir Ribeiro Tavares, Orestes Vicente Forlenza, Moacir Fernandes de Godoy, Gerardo Maria de Araújo Filho","doi":"10.2174/0115672050468989260629094050","DOIUrl":"https://doi.org/10.2174/0115672050468989260629094050","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease stands as the most prevalent form of dementia, characterized by a progressive decline in cognitive function and memory. Numerous risk factors have been linked to its development, creating a complex interplay of influences. In this study, we aim to delve into the relationship between cardiovascular disease and Alzheimer's disease, exploring how conditions affecting heart health may impact the onset and progression of this debilitating neurological disorder. Through this research, we could find potential connections that inform prevention strategies and therapeutic approaches.</p><p><strong>Materials and methods: </strong>We adopted the PRISMA guidelines and defined the PECOS framework as follows: Population (P) = individuals; exposure (E) = cardiovascular disease; comparison (C) = without cardiovascular disease; outcome (O) = Alzheimer's disease; and study design(S) = all kinds of studies with an association between cardiovascular disease and Alzheimer's disease without time limits. A meta-analysis was conducted using case-control, cohort, and genetic studies to estimate Odds Ratios (ORs) or Hazard Ratios (HRs).</p><p><strong>Results: </strong>The pooling of data in meta-analysis demonstrated that a person with any Cardiovascular Disease (CVD), Heart Failure (HF), Coronary Artery Disease (CAD), Atrial Fibrillation (AF), Hypertension (HTN), and Myocardial Infarction (MI) had more risk of developing Alzheimer's disease [CVD: HR = 1.30 (CI: 1.27-1.33) / HF: HR = 1.63 (CI: 1.37-1.94) / CAD: HR = 1.43 (CI: 1.40-1.46) / AF: HR = 1.38 (CI: 1.34-1.42) / HTN: HR = 1.22 (CI: 1,10-1.35) / MI: HR = 1.07 (CI: 1,01-1.13)]. Cross-sectional studies demonstrated an association between cardiovascular diseases and Alzheimer's disease [OR = 1.29 (CI: 1.23-1.35)]. Mendelian randomization meta-analysis did not demonstrate a causal relation between cardiovascular disease and Alzheimer's disease [AF: OR = 1.03 (CI: 1.00-1.01) / HF: OR = 1.00 (CI: 0,79-1.36)]. A Mendelian randomization meta-analysis demonstrated that a person with AD had a higher risk of developing myocardial infarction [OR = 1.07 (CI: 1.03-1.10)].</p><p><strong>Discussion: </strong>This review examines the connection between AD and CVD, noting that HF increases the risk of developing AD with a hazard ratio of 1.63. It suggests that altered brain perfusion and hypoxia appear to be one important neurodegenerative factor. Some genetic changes in individuals with CVD made them more vulnerable to AD. Effective prevention and treatment of CVD can help reduce the risk of AD.</p><p><strong>Conclusion: </strong>HF, AF, and CAD were the CVDs with the highest risk of developing AD. The results suggest that changes in cerebral blood perfusion are a principal neuropathological event that leads to genetic alterations that end in AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521646","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":"Ganoderma sinense Polysaccharides Improve Cognition in a Mouse Model of Alzheimer's Disease by Modulating Gut Microbiota and Short-Chain Fatty Acid Metabolism.","authors":"Wei Li, Chunhe Guo, Yudi Jin, Hong Ji, Linbo Zhang, Wei Li, Wenhui Zhang, Lu Fu","doi":"10.2174/0115672050473800260622054102","DOIUrl":"https://doi.org/10.2174/0115672050473800260622054102","url":null,"abstract":"<p><strong>Introduction: </strong>The number of patients with Alzheimer's Disease (AD) worldwide is expected to reach 152 million by 2050, but developing an effective AD treatment remains challenging. This study purified two polysaccharides (GSP1 and GSP2) from Ganoderma sinense, a traditional Chinese medicine, and investigated their potential therapeutic effects against AD.</p><p><strong>Materials and methods: </strong>GSP1 and GSP2 were purified and characterized for key physicochemical properties, including monosaccharide composition and molecular weight. In vitro neuroprotective efficacy was evaluated using glutamate-challenged SH-SY5Y cells. For in vivo assessment, an AlCl₃/D-galactose induced AD mouse model was established to quantify cognitive/memory enhancement. Multiomic analysis of the gut microbiota, Short-Chain Fatty Acid (SCFAs) metabolomics, and behavioural tests were conducted to elucidate the therapeutic mechanisms of GSP1.</p><p><strong>Results: </strong>Both GSP1 and GSP2 conferred neuroprotection against toxin-induced damage. Notably, GSP1 demonstrated superior efficacy compared with GSP2, significantly enhancing cognitive/ memory performance and reducing amyloid-β plaque deposition. Furthermore, GSP1 changed gut microbial diversity and SCFA metabolic profiles. Critical genus-level correlations emerged: Turicibacter, Jeotgalicoccus, and Staphylococcus were positively associated with therapeutic outcomes, whereas Odoribacter was negatively associated.</p><p><strong>Discussion: </strong>Natural polysaccharides, particularly GSP1, demonstrate therapeutic potential against AD by modulating gut microbiota. Mechanistically, this effect is linked to reshaping microbial communities and affecting the production of neuroprotective SCFAs. Although these findings position GSP1 as a promising AD therapeutic candidate, deeper exploration of gut-brain axis mechanisms remains essential for clinical translation.</p><p><strong>Conclusion: </strong>GSP1 emerges as a promising therapeutic candidate for AD, offering a new approach to developing AD-targeted pharmaceuticals and nutraceuticals.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551974","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":"Cerebral Glucose Hypometabolism in Alzheimer's Disease: A Meta-Analysis and Transcriptomic-Neuroimaging Study.","authors":"Chu-Xin Huang, Yi Pan, Han Xiao, Jing-Hang Wang, Jun Liu","doi":"10.2174/0115672050470646260624045159","DOIUrl":"https://doi.org/10.2174/0115672050470646260624045159","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebral glucose hypometabolism is known to occur in Alzheimer's Disease (AD). However, the spatial pattern of these metabolic alterations remains inconsistent across studies, and the molecular mechanisms linking regional metabolic vulnerability to gene expression profiles are poorly understood, thus highlighting the neuroimaging-transcriptomics gap.</p><p><strong>Methods: </strong>We performed a coordinate-based meta-analysis of 18F-fluorodeoxyglucose positron emission tomography data from 17 studies. This involved 888 AD individuals and 529 healthy controls. Spatial correlation analysis of metabolic alterations and transcriptomic gene data from the Allen Human Brain Atlas was performed. Enrichment analysis was conducted to explore biological processes associated with the identified genes.</p><p><strong>Results: </strong>Compared with healthy controls, AD patients showed significant glucose hypometabolism in regions including the bilateral precuneus, median cingulate/paracingulate gyri, posterior cingulate gyri, angular gyri, inferior parietal gyri, supramarginal gyri, middle occipital gyri, middle temporal gyri, inferior temporal gyri, the left inferior frontal gyrus (triangular part), and anterior cingulate/ paracingulate gyrus. Spatial correlation analysis revealed that these changes were correlated with 2,701 genes. The identified genes were mainly involved in biological processes such as the DNA metabolic process, chromatin remodeling, chromatin/kinase binding, and mitochondrion organization.</p><p><strong>Discussion: </strong>The meta-analysis and transcriptomic-neuroimaging study revealed consistent patterns of brain metabolism and AD-associated gene sets. We also identified related biological processes. These results link microscale gene expression to macroscale glucose hypometabolism and offer new mechanism perspectives.</p><p><strong>Conclusion: </strong>This study maps AD-related glucose hypometabolism to specific transcriptional profiles, providing novel insights into the molecular basis of metabolic alterations in AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458223","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":"Diagnostic Accuracy of Plasma p-tau181 Measured Using Automated Chemiluminescent Immunoassays for Alzheimer's Disease: A Systematic Review and Meta-Analysis.","authors":"Zhongshuang Hu, Yuxin Su, Jiayun Xi, Jiao Li","doi":"10.2174/0115672050477953260623073513","DOIUrl":"https://doi.org/10.2174/0115672050477953260623073513","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate the diagnostic accuracy of plasma p-tau181 measured on fully automated immunoassay platforms for detecting Alzheimer's Disease (AD), and to determine how performance varies according to the reference standard used to define AD pathology.</p><p><strong>Materials and methods: </strong>A systematic search was conducted across major databases for studies reporting the diagnostic accuracy of plasma p-tau181. Eligible studies enrolled adults across the Alzheimer's disease continuum and applied either CSF Aβ42/40, combined CSF Aβ42/40 and ptau181, or clinical diagnostic criteria as the reference standard. Data were synthesized using random- effects models. HSROC modeling was applied to estimate pooled sensitivity, specificity, and AUC.</p><p><strong>Results: </strong>A total of 19 studies involving 4266 participants were included. Most studies (18/19) used the Lumipulse platform, whereas only 1 study used Elecsys. Therefore, the pooled estimates mainly reflect Lumipulse-based evidence. Pooled sensitivity and specificity were 0.81 and 0.77 (AUC 0.84) when CSF Aβ42/40 defined amyloid pathology. When combined, CSF amyloid and tau positivity was required; sensitivity and specificity were 0.83 and 0.78 (AUC 0.86). Using clinical diagnostic criteria, pooled sensitivity reached 0.92, with a specificity of 0.78 (AUC 0.84). However, these subgroup estimates should be interpreted cautiously because substantial between-study heterogeneity remained, and some subgroups contained only a small number of datasets.</p><p><strong>Discussion: </strong>P-tau181 measured by automated chemiluminescent immunoassays showed promising diagnostic performance across reference standards, but the summary estimates are influenced by substantial heterogeneity and should not be interpreted as universally transferable measures of performance.</p><p><strong>Conclusion: </strong>The results support plasma p-tau181 as a promising scalable biomarker for AD. However, because the available evidence is predominantly derived from Lumipulse-based studies, it remains insufficient to determine whether comparable performance extends to other automated CLIA platforms.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400262","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}