Current Alzheimer research最新文献

{"title":"Transitioning from Clinical Trial to Clinical Practice for Long-Term Lecanemab Treatment in Early Alzheimer's Disease: Perspectives from a Cohort Study from the Alzheimer's Research and Treatment Center.","authors":"David Watson, Michael G Neam, Mark Stafford, Cynthia Bouchard, Venessa Ranney, Sydney Werner","doi":"10.2174/0115672050525938260923072703","DOIUrl":"https://doi.org/10.2174/0115672050525938260923072703","url":null,"abstract":"<p><strong>Introduction/background: </strong>Lecanemab, an anti-amyloid monoclonal antibody, significantly reduces amyloid markers and slows clinical decline in early Alzheimer's disease (AD) clinical trials. We assessed our single-center experience with lecanemab, including evaluating efficacy and safety data as well as patient-reported outcomes of individuals from our single center treated with intravenous or subcutaneous lecanemab.</p><p><strong>Materials and methods: </strong>We conducted a single-center, nested cohort study of early AD subjects on lecanemab (intravenous or subcutaneous) at our center. Participants had been initiated on lecanemab therapy as part of lecanemab Study 201 or Clarity AD, and then continued lecanemab treatment in our center. Data collection included patient demographic characteristics, efficacy (eg, CDR-SB), safety, and patient-reported outcomes from surveys.</p><p><strong>Results: </strong>At our center, 136 people were randomized to receive either lecanemab or placebo in either lecanemab Study 201 (lecanemab:53; placebo:16) or Clarity AD (lecanemab:37; placebo:30). Patients receiving lecanemab were more likely to have higher rates of stable or improved disease across efficacy assessments relative to placebo. There were no new long-term safety signals, and the most common adverse events for lecanemab patients were infusion-related reactions (36.2%), ARIA-H (25.9%), and ARIA-E (13.8%). Survey responses demonstrated high satisfaction with the subcutaneous lecanemab administration, including with treatment satisfaction (97%) and convenience (97%). All patients preferred subcutaneous over IV dosing, citing quickness, ease, and comfort.</p><p><strong>Discussion: </strong>Our single-center experience with long-term lecanemab treatment was similar to that observed in clinical trials.</p><p><strong>Conclusion: </strong>The subcutaneous lecanemab formulation was highly preferred by patients and care partners, with feedback highlighting reduced treatment burden and strong acceptability.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187396","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":"Global Dynamics and Emerging Trends in Alzheimer's Disease and Apoptosis from 2007 to 2025: A Bibliometric Analysis of Scholarly Evolution.","authors":"Yan Jiang, Xiaolin Li, Peiyun Yue, Yuanli Hu, Xiaoyu Lan, Xinrui Yang, Mingtai Chen, Yuanyuan Li, Gang Luo, Mengnan Liu, Jinwen Wu","doi":"10.2174/0115672050512147260928102334","DOIUrl":"https://doi.org/10.2174/0115672050512147260928102334","url":null,"abstract":"<p><strong>Introduction: </strong>To conduct the first systematic bibliometric analysis of global research on the relationship between Alzheimer's disease (AD) and apoptosis from 2007 to 2025.</p><p><strong>Methods: </strong>This study utilized the Web of Science Core Collection (WoSCC) and Scopus to retrieve literature from 2007 to 2025 concerning the role of apoptosis in Alzheimer's disease. Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, SCImago Graphica, and Bibliometrix R software packages.</p><p><strong>Results: </strong>China produced the most papers (n=823), though co-authorship led to duplicate counting. Leading institutions included China Medical University and Huazhong University of Science and Technology; Harvard University had the highest academic impact. The Journal of Biochemistry was the most active and cited journal. Dr. Zhang Y was the most prolific author, and Dr. Wang H the most cited.</p><p><strong>Discussion: </strong>China and the United States are dominant contributors, but Chinese research remains domestically oriented with lower international citation impact. The Journal of Alzheimer's Disease serves as a key dissemination platform. Major research themes include Aβ-induced mitochondrial dysfunction, oxidative stress, tau hyperphosphorylation synergizing with apoptosis, and emerging multi-target therapies. Recent attention has shifted towards inflammation, synaptic impairment, and combined strategies. The vicious cycles between Aβ and oxidative stress, and between tau pathology and apoptosis, warrant further mechanistic investigation.</p><p><strong>Conclusions: </strong>This study provides a systematic summary of research on AD and apoptosis. β- amyloid (Aβ) and abnormal Tau phosphorylation are likely to remain central areas of focus for future research.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187314","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":"Tetrachloro-1,4-benzoquinone Exerts Neurotoxicity through Neuroinflammation and the TLR4 Signaling Pathway, which is a Risk Factor for Alzheimer's Disease: An Integrated Network and Mendelian Randomization Analysis.","authors":"Min Li, Shijie Lv, Lexiang Cui, Shaokuan Fang","doi":"10.2174/0115672050502048260925094031","DOIUrl":"https://doi.org/10.2174/0115672050502048260925094031","url":null,"abstract":"<p><strong>Introduction: </strong>Research has found that the disinfection byproduct Tetrachloro-1,4- Benzoquinone (TCBQ) in drinking water increases the risk of Alzheimer's Disease (AD). However, the mechanism by which TCBQ increases the risk of AD remains unclear.</p><p><strong>Methods: </strong>This study employs a comprehensive approach that includes network toxicology (PPI network, hub genes, KEGG analysis), Mendelian randomization, computational simulations (molecular docking and dynamics), and cellular experiments to systematically elucidate the neurotoxic mechanisms of TCBQ.</p><p><strong>Results: </strong>Key findings indicate that TCBQ induces neurotoxicity by activating the Toll-like receptor signaling pathway, AD, and the apoptosis pathway. All ligand-receptor docking energies are recorded at ≤ -1.8 kcal/mol, suggesting that TCBQ demonstrates a stable interaction with the targets. Molecular simulations confirm that TCBQ tightly binds to targets such as Caspase3 and TLR4. Mendelian randomization found that XDH, FABP3, IMPDH1, ACBD7, and CASP3 are common targets and play a potential role in AD. Immunofluorescence experiments revealed that APP expression increased after TCBQ treatment. Cellular experiments verified that TCBQ significantly upregulates the expression of inflammation- and apoptosis-related proteins, including IL-1B, MyD88, NFκB, TLR4, Cleaved-Caspase3, and Cyt C, leading to neuronal cell death. Notably, the TLR4 inhibitor effectively reversed the expression of these proteins and alleviated cell death.</p><p><strong>Discussion: </strong>The discussion indicates that TCBQ induces neurotoxicity by activating the TLR4 pathway and apoptotic signals, and Caspase3 is a potential co-target. TLR4 inhibitors can reverse protein alterations and cell death, suggesting that intervention in this pathway may alleviate TCBQrelated nerve damage.</p><p><strong>Conclusion: </strong>Our research provides a theoretical basis for the clinical assessment of potential neurotoxicity risks in populations exposed to TCBQ.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187398","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":"Genetic Evidence of Association Between Plasma Cathepsin L2 and Alzheimer's Disease: A Mendelian Randomization Study.","authors":"Weibo Tian, Yitong Hao, Siqi Qiu, Zhe Chen, Xuelian Wu, Yu Yang","doi":"10.2174/0115672050504771260920194040","DOIUrl":"https://doi.org/10.2174/0115672050504771260920194040","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have suggested cathepsins, lysosomal cysteine proteases, are associated with Alzheimer's DISEASE (AD). This study conducted Mendelian Randomization (MR) analysis to systematically assess the causal effect of genetically predicted plasma cathepsins levels on AD and AD endophenotypes (cognition and brain structure).</p><p><strong>Method: </strong>Recent large-scale Genome-Wide Association Studies (GWAS) in Europe provided summary statistics on plasma cathepsins, AD, cognition, and brain structure. The primary statistical estimate was employed by Inverse Variance Weighting (IVW). Various sensitivity analysis was performed to draw robust results, including Cochran's Q test, MR-Egger intercept test, and MR PRESSO.</p><p><strong>Results: </strong>Genetically predicted plasma cathepsin levels were not significantly associated with AD risk. Higher genetically predicted cathepsin L2 levels were associated with better fluid intelligence (β = 0.081, 95% CI 0.029 to 0.133, P = 0.00230, adjusted P = 0.0207). The associations of cathepsin L2 with general cognitive function (β = 0.081, 95% CI 0.010 to 0.152, P = 0.0247, adjusted P = 0.2226) and white matter hyperintensity volume (WMH, β = -0.068, 95% CI -0.134 to -0.002, P = 0.0433, adjusted P = 0.3898) were considered exploratory. Cathepsin L2 was also associated with monocyte count after correction across the three evaluated immune-cell traits (nominal P = 0.0133, FDR-adjusted P = 0.0285); the estimated indirect effect through monocyte count was -0.0016.</p><p><strong>Discussion: </strong>These findings identify cathepsin L2 as the most consistently associated candidate with fluid intelligence and additional exploratory signals across cognitive, neuroimaging, and peripheral immune-cell phenotypes. The association with monocyte count raises a testable hypothesis regarding a peripheral immune-related pathway. Further studies using larger protein GWAS datasets, stronger genetic instruments, and independent populations are required to validate these findings.</p><p><strong>Conclusion: </strong>Genetically predicted plasma cathepsin L2 levels were associated with fluid intelligence after multiple comparisons. Although the immune-cell analyses raised the possibility of a monocyte-related peripheral pathway, the present findings did not establish a statistically supported mediating effect or a direct protective effect of cathepsin L2 against AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121570","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":"Immunity and Inflammation in Alzheimer's Disease: A Narrative Review on Mechanisms and Therapeutic Prospects.","authors":"Lulan Chi, Fengqing Xu, Xiaoying Dai, Zhanrui Li, Jingjie Li, Zheng Li","doi":"10.2174/0115672050493089260903062914","DOIUrl":"https://doi.org/10.2174/0115672050493089260903062914","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is an age-related neurodegenerative disorder of the Central Nervous System (CNS), characterized by amyloid-β (Aβ) deposition and Neurofibrillary Tangles (NFTs) caused by the hyperphosphorylation of tau protein. Neuroinflammation is an increasingly recognized feature of AD, playing a critical role in disrupting the immune microenvironment within the brain parenchyma. High levels of various inflammatory mediators have been documented in both AD patients and experimental AD models. Similarly, multiple immune cells have been found to accumulate in the brain parenchyma, the meninges, and the choroid plexus. Therefore, antiinflammatory therapies, including Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and immune regulatory strategies hold promise as potential novel approaches for the prevention and treatment of AD. Currently, a variety of anti-inflammatory agents and immunotherapies have demonstrated efficacy in AD animal models, and several clinical trials of immunotherapeutic interventions have been completed or are underway. This review systematically summarizes the core pathophysiological mechanisms by which inflammatory and immune dysfunctions contribute to AD pathogenesis and explores potential therapeutic interventions targeting these mechanisms, thereby providing theoretical insights for clinical translational research on AD treatment.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019330","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":"Vitamin C versus Alzheimer's Disease. Commentary on the Effect of Ascorbic Acid on the Transgenic Drosophila Expressing Human Aβ-42 in the Neurons.","authors":"Ryszard Pluta, Marzena Ułamek-Kozioł","doi":"10.2174/0115672050513704260903053055","DOIUrl":"https://doi.org/10.2174/0115672050513704260903053055","url":null,"abstract":"<p><p>A recent article by Siddique et al. published in Current Alzheimer's Research suggests that vitamin C may have a neuroprotective effect in Alzheimer's disease, which inspired us to write this commentary. In this commentary, we focus on the effects of vitamin C treatment on amyloid in a transgenic Drosophila melanogaster model of Alzheimer's disease. It should be noted that some of the information presented in this article raises more questions than it answers. The article does not provide a clear answer to the question posed in the title. We note that the authors demonstrated, to a very limited extent, the ameliorative effects of vitamin C on oxidative stress, cholinergic function, improved behavior, and prolonged lifespan, yet their enthusiasm for the therapeutic potential of vitamin C in Alzheimer's disease has not faded. In conclusion, the work contains controversial and speculative statements; therefore, drawing far-reaching conclusions and applying vitamin C to Alzheimer's disease are not justified by the available evidence.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019400","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":"Basic Research on the Lymphatic System and Exploratory Research in LVA Surgery for Alzheimer's Disease.","authors":"Shi Wenxin, Zheng Youmao, Huang Wenhua","doi":"10.2174/0115672050503391260907045733","DOIUrl":"https://doi.org/10.2174/0115672050503391260907045733","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's Disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive decline. Its characteristic pathological features include Aβ plaque deposition and abnormal tau protein aggregation. Biomarker testing has improved AD diagnosis. However, current treatments are primarily symptomatic, and no effective therapies are available to slow disease progression.</p><p><strong>Materials and methods: </strong>In this review, PubMed, CNKI, Wanfang Data, and the Chinese Medical Journal Full-text Database were searched using core terms including lymphatic system, Alzheimer's disease, and deep cervical lymphatic-venous anastomosis with supplementary synonyms. After deduplication and two-round screening, irrelevant, duplicate, low-quality, and non-full-text articles were excluded, and eligible literature was systematically summarized.</p><p><strong>Results: </strong>The proposal of the glymphatic system has refined the theory of cerebral fluid circulation and waste clearance. Its dysfunction is closely associated with neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD), providing a novel target for AD treatment. Deep cervical Lymphatic-Venous Anastomosis (LVA), as an emerging surgical approach with potential to alleviate AD symptoms, has been initially validated for its short-term efficacy. However, it is still in the early stage of clinical exploration, and further systematic research is required for its successful clinical translation.</p><p><strong>Discussion: </strong>The glymphatic system mediates brain fluid circulation and waste clearance, providing new insights into AD pathogenesis and treatment. Building on this understanding, deep cervical Lymphatic-Venous Anastomosis (LVA) has emerged as a promising surgical intervention to alleviate AD pathology. Nevertheless, the considerable technical demands and incompletely elucidated mechanism of LVA severely limit its clinical translation, rendering these challenges a central research priority.</p><p><strong>Conclusion: </strong>Breakthroughs in the central lymphatic system have provided an important direction for exploring the pathological mechanisms of AD and developing innovative therapeutic strategies. Clarifying the theoretical basis and technical evolution of LVA surgery, as well as addressing relevant controversial issues, constitutes a key focus to advance the basic research and clinical translation of AD treatment.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013478","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":"Novel Amyloid-β Aggregation Inhibitors Based on Phenylalanine Structure.","authors":"Mingming Xu, Hongmin Wang, Shihong Li, Junjie Ye, Yuanjun Sun, Yidan Xu, Haiyan Zhang, Weimin Zhao, Jingjing Zhang","doi":"10.2174/0115672050489243260827065622","DOIUrl":"https://doi.org/10.2174/0115672050489243260827065622","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) aggregation, making its inhibition a promising therapeutic strategy. This study evaluated the effects of two phenylalanine derivatives on Aβ aggregation and associated neurotoxicity.</p><p><strong>Methods: </strong>Interactions between Aβ monomer and two compounds (12a and 5g) were explored by molecular docking. The inhibitory effects of the compounds on Aβ aggregation were evaluated using a thioflavin-T (ThT) assay, transmission electron microscopy (TEM), and dot blot. The neuroprotective ability of the two compounds was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay.</p><p><strong>Results: </strong>Docking analysis revealed that compounds 12a and 5g can bind to monomeric Aβ and identified the amino acids responsible for the interactions. The two compounds significantly reduced ThT fluorescence during the 48-hour incubation at all concentrations in ThT kinetics assays. The inhibitory effects were further confirmed in TEM. Both compounds suppressed Aβ oligomerization (reductions to 42.72% and 35.90% of the untreated control group, respectively). Furthermore, compound 5g, with a new structure, showed remarkable protection (cell viability increased to 97.86% of the control) against Aβ oligomer-treated human neuroblastoma SH-SY5Y cells, while having no intrinsic effect on cell viability.</p><p><strong>Discussion: </strong>Compounds 12a and 5g act as more specific Aβ oligomerization inhibitors than traditional polyphenols such as (-)-epigallocatechin-3-gallate (EGCG). The results may provide molecular insights for the rational design of potent Aβ aggregation inhibitors for AD therapy.</p><p><strong>Conclusion: </strong>This study demonstrates that phenylalanine derivatives hold great promise as novel AD therapeutic leads.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Epoxyeicosatrienoic Acid Signaling in Advanced-Stage Alzheimer's Disease (Investigation of Epoxyeicosatrienoic Acid Levels in Patients with Advanced Alzheimer's Disease).","authors":"Serpil Erşan, Esma Özmen, İsmail Sari, E Erdal Erşan","doi":"10.2174/0115672050468773260821110356","DOIUrl":"https://doi.org/10.2174/0115672050468773260821110356","url":null,"abstract":"<p><strong>Introduction: </strong>The study aimed to compare plasma Epoxyeicosatrienoic Acid (EET) isomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) in patients with advanced-stage late-onset Alzheimer's Disease (AS-LOAD) versus healthy controls matched by age and sex.</p><p><strong>Methods: </strong>In this cross-sectional case-control study, 30 patients with AS-LOAD were compared with 30 cognitively healthy (control) individuals. Plasma EET levels were analyzed by liquid chromatography coupled with Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>Plasma concentrations of all measured EET regioisomers were significantly lower in patients with AS-LOAD compared with controls. Significant reductions were observed for 14,15-EET (p = 0.007), 11,12-EET (p = 0.001), 8,9-EET (p = 0.007), and 5,6-EET (p = 0.011).</p><p><strong>Discussion: </strong>EETs are reportedly implicated in AD development, with most previous investigations using animal models and targeted enzymes involved in EET metabolism, particularly soluble epoxide hydrolase (sEH). Furthermore, no studies have specifically examined EET metabolism in patients with advanced AD. This study revealed defective EET signaling with consequent increased sEH activity in AS-LOAD, suggesting that decreased EET might contribute to tau-mediated neurodegeneration, oxidative stress, and neuroinflammation in these patients.</p><p><strong>Conclusion: </strong>This study emphasizes the crucial role of EETs in AD pathology. Targeting EET metabolism could offer a promising therapeutic strategy for preventing AD. Studies that track disease progression are therefore a prerequisite for delaying its disease onset; thus, larger-scale longitudinal studies are needed to confirm these findings.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946462","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":"Decoding Frontotemporal Dementia: Genes, Proteins and Prospects for Precision Medicine.","authors":"Kaushik Raj, Nandani Kumari, Pragya Bharti, Ranjeet Kumar, Dharmendra Kumar","doi":"10.2174/0115672050478591260821105132","DOIUrl":"https://doi.org/10.2174/0115672050478591260821105132","url":null,"abstract":"<p><p>Frontotemporal Dementia is an umbrella term for several neurodegenerative disorders that have a similar presentation pattern, which is accompanied by neural damage and brain tissue loss in the frontal and temporal regions. Recent studies have observed that the heterogeneity of Frontotemporal Dementia (FTD) is reflected in clinical features, genetics, and molecular perspectives. Specifically, the major forms of pathology in FTD are linked to abnormal protein accumulation, which includes tau, TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS). Moreover, genetic research on FTD has identified vital mutations in MAPT (Microtubule-associated protein Tau), GRN (Progranulin Gene), and C9ORF72 genes (Chromosome 9 open reading frame genes). Recent developments in neuroimaging, biomarker levels in body fluids, and molecular profiling have increased diagnostic precision, enabling earlier detection of disease subtypes. Neurofilament light chain (NfL), progranulin, and several other biomarkers, together with novel neuroimaging approaches, are currently being applied for disease classification, prognosis, and disease treatment monitoring. These developments have accelerated the application of precision medicine for FTD, including antisense oligonucleotides, progranulin-restorative drugs, tau-specific therapies, and gene therapy. Despite advances in elucidating the biology of FTD, no disease-modifying therapies have yet been developed, and treatments remain symptomatic until now. Undoubtedly, there are many challenges when taking into account variable presentation, overlapping pathologies, and the lack of robust biomarkers. The aim of this paper is to provide an in-depth analysis of the epidemiology, clinical features, molecular pathologies, biomarkers, and potential therapeutic approaches concerning FTD, with a particular emphasis on the growing role of precision medicine. Omics technologies, biomarker- based patient stratification, and hypothesis-driven clinical trials are undoubtedly essential steps towards personalized therapy for FTD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908582","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}