Current Alzheimer research最新文献

{"title":"Advances in Nose-to-Brain Delivery Systems for Effective Alzheimer's Disease Management.","authors":"Alka Sahu, Khileshwari, Kavita Patle, Parag Jain, Ajazuddin","doi":"10.2174/0115672050395356251106100427","DOIUrl":"10.2174/0115672050395356251106100427","url":null,"abstract":"<p><p>Neurodegenerative diseases comprise a heterogeneous group of disorders characterized by the progressive structural and functional deterioration of neurons in the central nervous system. Among them, Alzheimer's disease is the most prevalent worldwide. Despite their distinct clinical manifestations, many neurodegenerative disorders share convergent pathophysiological mechanisms such as protein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, and neuroinflammation, which ultimately drive neuronal loss. These processes lead to profound impairments in cognitive performance, motor coordination, and overall functional capacity, making such diseases exceptionally difficult to diagnose early and manage effectively.. Traditional treatment approaches administered orally or parenterally face limitations, including high hepatic metabolism, poor penetration across the blood-brain barrier (BBB), and systemic side effects. This review highlights the potential of the nose-to-brain (N2B) delivery system as an emerging and promising therapeutic strategy. N2B delivery utilizes the olfactory and trigeminal nerve pathways in the nasal cavity to rapidly and precisely deliver drugs to the central nervous system without crossing the blood-brain barrier. Because the system is non-invasive, it offers high bioavailability, reduced systemic exposure, and improved patient compliance. The use of lipid nanocarriers, nanoparticles, dendrimers, and nanogels to enhance the stability of drugs, facilitating efficient targeting and controlled release, is a crucial factor in optimizing N2B drug delivery systems. Various attributes influence drug transport, which are physiological, physicochemical and formulation-dependent characteristics. The main challenges faced by the N2B delivery system are enzymatic degradation and mucociliary clearance. Emerging technologies, such as AI, 3D Printing, and personalized medicine, all hold promise for future inventions in this area. Preclinical and clinical trials demonstrate the efficacy of delivering N2B in treating neurodegenerative diseases; however, its full potential remains to be seen due to regulatory, safety, and scalability concerns. Hence, this review emphasizes the research required to pursue interdisciplinary collaboration and unlock the full potential of N2B delivery, as well as a new approach to transforming neurodegenerative conditions.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"225-244"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055940","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":"Clinical and Medication Factors Associated with Cognitive Decline in Dementia: A Healthcare Database Study.","authors":"Chen-Chih Chung, Jia-Hung Chen, Lung Chan, Hung-Yi Liu, Joni Yu-Hsuan Shao, Yi-Chieh Hung, Chien-Tai Hong","doi":"10.2174/0115672050420540251027112136","DOIUrl":"10.2174/0115672050420540251027112136","url":null,"abstract":"<p><strong>Introduction: </strong>Dementia is the most common neurodegenerative disease, but the risk factors associated with its progression remain incompletely understood. Identifying clinical and medication-related determinants of cognitive decline may inform patient management and guide treatment strategies.</p><p><strong>Materials and methods: </strong>Individuals with dementia who underwent paired Mini-Mental State Examination (MMSE) assessments between 2013 and 2019 were identified from the Taipei Medical University Clinical Research Database. To ensure adequate follow-up, paired assessments were required to be at least 90 days apart, with an actual mean follow-up interval of 21.5 ± 18.0 months. Demographic data, comorbidities, medication prescriptions, and blood biochemistry results were extracted. Generalized estimating equations were applied to evaluate associations between these factors and MMSE changes.</p><p><strong>Results: </strong>A total of 3,054 individuals with dementia were included (mean age 78.0 ± 9.2 years, 61.1% women). The mean baseline MMSE score was 18.5 ± 6.7 and it declined to 16.0 ± 7.5 at follow-up. Male sex was significantly associated with greater MMSE decline (estimate: -0.920, 95% CI: -1.552 to -0.289, p = 0.004). Antidementia medications were significantly associated with less decline in MMSE scores (estimate: 1.245, 95% CI: 0.676 to 1.815, p < 0.001). In contrast, non-aspirin antiplatelet agent use was associated with a greater decline among men (estimate: -1.346, 95% CI: -2.518 to -0.173, p = 0.025).</p><p><strong>Discussion: </strong>These findings highlighted that both clinical and pharmacological factors influence cognitive decline in dementia. Antidementia medications were linked to slower deterioration, supporting their role in disease management. Conversely, the association of non-aspirin antiplatelet agents with faster decline in men suggested potential adverse effects that warrant further investigation.</p><p><strong>Conclusion: </strong>In this large real-world cohort, sex and medication use were key determinants of cognitive decline in dementia. Antidementia medications mitigated decline. Notably, only non-aspirin antiplatelet agents, but not aspirin, were associated with greater cognitive decline in men., underscoring the need for personalized treatment approaches.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"209-217"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055929","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":"A Multimodal Framework for Alzheimer's Prevention: Diet, Exercise, Fasting, Sleep, and Gut Microbiota.","authors":"Shubham Kurmi, Sanket Shirodkar, Siddhi Bagwe Parab, Gaurav Doshi","doi":"10.2174/0115672050467997260323164241","DOIUrl":"10.2174/0115672050467997260323164241","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) and related dementias arise from a multifactorial interplay of genetic susceptibility, metabolic dysfunction, neuroinflammation, and lifestyle determinants. With limited disease-modifying pharmacotherapies, lifestyle interventions have emerged as compelling, evidence-based avenues for prevention and early management. This review integrates mechanistic, translational, and clinical insights on major modifiable behaviours, physical activity, diet, intermittent fasting, sleep regulation, and gut-microbiome-based approaches that collectively shape cognitive ageing. Aerobic, anaerobic, and resistance exercises exert neuroprotective effects by activating BDNF-TrkB signalling, enhancing hippocampal neurogenesis, improving synaptic plasticity, and stimulating peripheral myokines (CTSB, IGF-1, GPLD1) that cross the blood-brain barrier to support neuronal resilience. Dietary interventions such as the Mediterranean, Mediterranean- DASH Intervention for Neurodegenerative Delay (MIND), and ketogenic diets mitigate AD pathology by reducing oxidative stress, inhibiting Aβ deposition, improving mitochondrial efficiency, and modulating APOE4-linked metabolic vulnerability. Intermittent fasting induces a metabolic shift toward ketone utilisation, activates autophagy pathways (AMPK, SIRT3, Nrf2), remodels the gut microbiome, and promotes angiogenesis through GDF11 signalling. The gut-brain axis contributes to cognitive health through microbial metabolites, such as Short-Chain Fatty Acids (SCFAs), tryptophan derivatives, modulation of neuroinflammation, and enhanced neuronal survival. Meanwhile, sleep quality, particularly slow-wave sleep, optimises glymphatic clearance and prevents the pathological accumulation of Aβ and tau. Collectively, the evidence suggests that multidomain lifestyle approaches offer synergistic benefits that exceed those of individual interventions, representing promising strategies for delaying cognitive decline. However, gaps remain regarding dose-response relationships, personalised protocols for APOE4 carriers, and long-term validation in diverse populations. Strengthening these research directions is crucial for integrating lifestyle medicine into preventive neurology and public health frameworks.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"349-366"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848424","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":"miRNAs: Promising Biomarkers for Alzheimer's Diagnosis and Treatment.","authors":"Mingyang Cai, Siru Yan, Yaxuan Sun, Qing Huo, Xueling Dai","doi":"10.2174/0115672050427877251118111643","DOIUrl":"10.2174/0115672050427877251118111643","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque deposition, neurofibrillary tangles of hyperphosphorylated tau protein, and chronic neuroinflammation, leading to synaptic dysfunction and cognitive decline. Current diagnostic methods rely on clinical symptoms and limited biomarkers, while available treatments only provide symptomatic relief without halting disease progression. MicroRNAs (miRNAs), small non-coding RNAs of 19-22 nucleotides, have emerged as crucial regulators of gene expression through post-transcriptional mechanisms and show distinct dysregulation patterns in AD patients' blood, cerebrospinal fluid (CSF), and brain tissues. Key miRNAs such as miR-132, miR-146a, miR-34a, and miR-125b demonstrate consistent alterations in expression levels, correlating with disease progression and offering potential as non-invasive diagnostic tools. This review comprehensively examines the dual role of miRNAs as diagnostic biomarkers and therapeutic targets for AD. We also provide an analysis of specific miRNA signatures in different biofluids (plasma, serum, CSF) and brain regions that correlate with disease stages, highlighting their potential for early and non-invasive diagnosis. Therapeutically, miRNAs modulate multiple AD-related pathways, including neuroinflammation via NF-κB signaling, Aβ production through BACE1 inhibition, and tau phosphorylation via GSK3β regulation. miRNAs also influence synaptic plasticity, mitochondrial function, and autophagy, presenting multifaceted opportunities for intervention. However, challenges, including miRNA heterogeneity, stability, and targeted delivery, remain critical impediments. Advances in nanocarriers, exosomal miRNAs, and viral vectors show promise in overcoming these obstacles, enabling precise miRNA modulation. In addition, we underscore the need for standardized protocols, further validation in clinical cohorts, and the development of cost-effective detection methods to translate miRNA-based approaches into practical diagnostics and therapies. By integrating miRNA biomarkers with existing diagnostic tools and exploring combinatorial therapeutic strategies, researchers can harness the potential of miRNAs to revolutionize AD intervention, paving the way for early detection and effective treatment of this devastating disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"123-137"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902153","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":"Relation between Cerebrospinal Fluid Catecholamines and Vascular Risk Factors, Thyroid Function and Vitamins in Healthy Individuals and Patients with Neurodegenerative Diseases.","authors":"Isabel Portela Moreira, Paula Serrao, Lucinda Sequeira, Maria José Sa, Maria Augusta Vieira-Coelho, Joana Guimaraes","doi":"10.2174/0115672050411466251014111557","DOIUrl":"10.2174/0115672050411466251014111557","url":null,"abstract":"<p><strong>Introduction: </strong>The locus coeruleus is the primary site of norepinephrine (NE) synthesis in the brain. Its dysfunction has been implicated in the pathogenesis of Alzheimer's disease. Vascular risk factors, thyroid dysfunction, and vitamin deficiencies have also been associated with an increased risk of dementia. This study aimed to evaluate the relationship between the catecholaminergic system-by measuring cerebrospinal fluid (CSF) levels of L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine (DA), and NE-and vascular risk factors, thyroid dysfunction, and vitamin deficiencies.</p><p><strong>Methods: </strong>We conducted a cross-sectional observational study in which CSF levels of L-DOPA, DA and NE were measured in 117 participants. Data on Blood Pressure (BP), heart rate, glycaemic and lipid profiles, smoking history, thyroid function and vitamin B12 and folic acid levels were collected for each participant.</p><p><strong>Results: </strong>We found significant correlations between NE and CSF glucose levels (r = 0.308, p = 0.003) in participants without diabetes mellitus, between L-DOPA and orthostatic variation of diastolic BP (r = -0.288, p = 0.014) and high-density lipoprotein (r = 0.404, p = 0.001) and between NE and triglycerides (r = 0.271, p = 0.030) and folic acid (r = 0.298, p = 0.009).</p><p><strong>Discussion: </strong>This is the first study to demonstrate correlations between CSF NE levels and CSF glucose, probably due to the effect of NE on astrocytes, and between CSF NE levels and folic acid, possibly related to its role in catecholamine synthesis. CSF L-DOPA levels were correlated with cardiovascular risk factors such as the orthostatic regulation of diastolic BP.</p><p><strong>Conclusion: </strong>These findings may contribute to a better understanding of the pathophysiology of neurodegenerative diseases.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"51-60"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902128","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":"Current Perspectives on Oxytocin and Alzheimer's Disease-Related Symptoms.","authors":"Anthony Modaffari, Sashana Dixon, Mamdouh Salman A Alsheri, Ana M Castejon","doi":"10.2174/0115672050403886251121065128","DOIUrl":"10.2174/0115672050403886251121065128","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a neurodegenerative disorder accounting for 60-80% of dementia cases globally. Several risk factors are associated with increased AD onset, including genetics, physical activity, and varying levels of social interaction. Extensive research has explored potential treatments for AD, among which oxytocin (OX) has shown beneficial effects on memory-related neurological processes. OX has been suggested to modulate neuroplasticity within the hippocampus in rat and mouse AD models. Further studies indicate that intranasal administration of OX may lead to significant improvements in memory and cognition. In addition, a non-peptide agonistic analogue, LIT-001, has been investigated. This review aims to provide insight into the potential of OX as a therapeutic target for AD and to explore alternatives that activate similar cellular signaling pathways.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"77-85"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937045","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":"Low-Dimensional Nanomaterials in Alzheimer's Disease: Current Applications.","authors":"Yijing Shi, Wen Luo, Yazhou Hu, Wanghua Chen","doi":"10.2174/0115672050413838251014045255","DOIUrl":"10.2174/0115672050413838251014045255","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's Disease (AD) is a common neurodegenerative disorder (NDD) driven by multifaceted pathologies, including β-amyloid (Aβ) aggregation, tau protein hyperphosphorylation, oxidative stress, metal ion dyshomeostasis, and neuroinflammation. Current therapeutic strategies remain limited by insufficient Blood-Brain Barrier (BBB) penetration, singletarget approaches, and inefficacy against nanoscale pathological aggregates. This review highlights the emerging potential of low-dimensional nanomaterials (LDNMs) as multi-target therapeutic platforms for AD.</p><p><strong>Methods: </strong>We systematically evaluate zero-dimensional (0D), one-dimensional (1D), and twodimensional (2D) nanostructures and establish a \"nano-nano\" interaction paradigm that demonstrates how LDNMs interact with AD core pathological factors. Supporting tables summarize experimental data quantifying the effects of LDNMs on Aβ and tau pathologies, oxidative stress, metal ion homeostasis, neuroinflammation, and the delivery of BBB-penetrant drugs.</p><p><strong>Results: </strong>LDNMs exhibit significant potential in mitigating core AD pathologies. They effectively inhibit Aβ aggregation and tau hyperphosphorylation, attenuate oxidative damage, restore metal ion homeostasis, reduce neuroinflammatory activity, and enable targeted drug delivery to the brain.</p><p><strong>Discussion: </strong>The multi-target functionality of LDNMs overcomes major limitations of single-target therapies. Their nanoscale dimensions and modifiable surfaces enable synergistic interactions with pathological factors, offering a holistic intervention strategy. Limitations and translational challenges are discussed for future research directions for clinical application.</p><p><strong>Conclusion: </strong>This review links the structure and drug loading of LDNMs to multi-targeted efficacy against core AD pathology. It establishes a mechanistic connection between nanomaterial size and multi-pathway efficacy that transcends the limitations of single-target strategies. Moreover, it also provides a comprehensive framework for designing LDNMs-based nanotherapeutics, highlighting their potential as multi-target platforms for AD therapy.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"1-36"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373490","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":"Corrigendum to: Advancing Alzheimer's Disease Diagnosis Using VGG19 and XGBoost: A Neuroimaging-Based Method.","authors":"Abdelmounim Boudi, Jingfei He, Isselmou Abd El Kader, Xiaotong Liu, Mohamed Mouhafid","doi":"10.2174/1567205023999260119151250","DOIUrl":"https://doi.org/10.2174/1567205023999260119151250","url":null,"abstract":"<p><p>The publisher identified that references 42 and 43 were duplicated in the published version of this article [1]. The error has now been corrected. The original article can be found online at: https://www.benthamscience.com/article/150567 Details of the error and the correction are provided below: Original: [42] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190, 110095. [43] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190: 110095. http://dx.doi.org/10.1016/j.compbiomed.2025.110095 PMID: 40158456 Corrected: [42] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190, 110095. http://dx.doi.org/10.1016/j.compbiomed.2025.110095 PMID: 40158456 [43] Olaimat MA, Bozdag S, Saeed F. TA-RNN: An attention-based time-aware recurrent neural network architecture to predict progression of Alzheimer's disease. Alzheimer's Dement 2024; 20(S1).</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":"23 1","pages":"76"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355293","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":"MicroRNA Signatures in Alzheimer's Disease and Normal-Tension Glaucoma: A Comparative Expression Analysis of miR-128 and miR-455-3p.","authors":"Mohammed Arish, Zabihollah Hashemzehi, Vahideh Baghaei, Alireza Maleki, Amir Masoud Salari, Saeid Rasouli, Mohammad Sedigh Dakkali","doi":"10.2174/0115672050425207251129073017","DOIUrl":"10.2174/0115672050425207251129073017","url":null,"abstract":"<p><strong>Introduction: </strong>The relationship between Alzheimer's disease (AD) and normal-tension glaucoma (NTG) is an emerging area of interest owing to shared neurodegenerative features. Nevertheless, few studies have ascertained circulating microRNAs (miR) across both conditions. This study aimed to compare the expression of miR-128 and miR-455-3p in patients with NTG and AD and in controls, and to explore their potential as circulating biomarker candidates.</p><p><strong>Materials and methods: </strong>In this cross-sectional study, serum miRNAs were extracted using a column- based kit and quantified by SYBR Green qRT-PCR (normalized to U6). Each reaction was run in triplicate. Data were analyzed via ANCOVA adjusted for age and sex, followed by Bonferroni post-hoc tests.</p><p><strong>Results: </strong>Both miR-128 and miR-455-3p were significantly upregulated in the AD and NTG groups compared with controls (p < 0.001 for both). Adjusted mean expression for miR-128 was approximately 2.1 in AD, 2.6 in NTG, and 0.3 in controls, while the corresponding miR-455-3p values were 2.9, 3.1, and 0.8, respectively. Post-hoc comparisons confirmed higher expression in both disease groups compared with controls, but not between AD and NTG. Power analysis revealed >0.99 power for group comparisons with controls, consistent with robust group-level differences.</p><p><strong>Discussion: </strong>miR-128 and miR-455-3p are implicated in neuronal stress responses, mitochondrial regulation, and amyloid-beta processing. Their parallel upregulation in AD and NTG suggests overlapping molecular signatures and may reflect systemic responses to neurodegenerative stress. These findings are also consistent with growing evidence that the eye and brain share vulnerability to similar cellular processes in neurodegeneration.</p><p><strong>Conclusion: </strong>Elevated serum miR-128 and miR-455-3p in both AD and NTG indicate overlapping expression profiles across conditions. These miRNAs may serve as promising circulating biomarker candidates and support the concept of a molecular interplay between ocular and cerebral pathologies. However, their diagnostic and mechanistic potential warrants validation in largescale, longitudinal studies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"218-224"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936321","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":"Quantitative Proteomic Analysis of APP/PS1 Transgenic Mice.","authors":"Jiayuan Wang, Xinyu Wang, Zihui An, Xuan Wang, Yaru Wang, Yuehan Lu, Mengsheng Qiu, Zheqi Liu, Zhou Tan","doi":"10.2174/0115672050345431241113112608","DOIUrl":"10.2174/0115672050345431241113112608","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD.</p><p><strong>Objective: </strong>The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD.</p><p><strong>Methods: </strong>To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts.</p><p><strong>Results: </strong>Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks.</p><p><strong>Conclusions: </strong>This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"339-348"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775967","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}