ACS Chemical Neuroscience最新文献

{"title":"Antidepressant-like Properties of a Selenium-Containing Pyridinium Salt Explored through In Vitro, In Vivo, and In Silico Approaches","authors":"Mariana Parron Paim,&nbsp;, ,&nbsp;Taís da Silva Teixeira Rech,&nbsp;, ,&nbsp;Letícia Devantier Krüger,&nbsp;, ,&nbsp;Larissa Sander Magalhães,&nbsp;, ,&nbsp;Filipe Penteado,&nbsp;, ,&nbsp;Caroline Signorini Gomes,&nbsp;, ,&nbsp;Eder João Lenardão,&nbsp;, ,&nbsp;César Augusto Brüning*,&nbsp;, and ,&nbsp;Cristiani Folharini Bortolatto*,&nbsp;","doi":"10.1021/acschemneuro.5c00233","DOIUrl":"10.1021/acschemneuro.5c00233","url":null,"abstract":"<p >Selenium (Se) compounds have demonstrated antioxidant and antidepressant-like effects; however, most reported molecules are highly lipophilic. In contrast, moderate water solubility is considered crucial for drug delivery and therapeutic application. Accordingly, Se-containing pyridinium salts emerge as promising candidates for depression treatment. In this study, we conducted a comprehensive evaluation of three Se-based pyridinium salts (designated as compounds <b>3A</b>, <b>3B</b>, and <b>3C</b>) using in vitro, in vivo, and in silico approaches. All three compounds exhibited cerebral antioxidant activity, significantly reducing lipid peroxidation and protein carbonylation in vitro. They also demonstrated in vitro inhibition of monoamine oxidase A and B in mouse brain tissue. Subsequently, an in vivo investigation with the salts using the tail suspension test in male Swiss mice (single intragastric dose of 5 mg/kg) identified compound <b>3B</b> as the most effective antidepressant-like agent. Further dose-response (0.5–5 mg/kg) and time-response (15–120 min) analyses established that the minimum effective dose was 1 mg/kg administered over 30 min. In silico ADMET predictions indicated favorable pharmacokinetic properties, and an acute oral toxicity study revealed that a 50-fold higher dose (50 mg/kg) than the therapeutic level did not produce any observable adverse effects. Taken together, these findings suggest that compound <b>3B</b> represents a promising antidepressant candidate for future studies.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 19","pages":"3713–3727"},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.5c00233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligopeptides and Polypeptides Impact Norepinephrine Detection in Lymphoid Tissue","authors":"Sarbeshwar Ojha,&nbsp;, ,&nbsp;Alexandra K. Brooke,&nbsp;, ,&nbsp;Blaise J. Ostertag,&nbsp;, ,&nbsp;Daniel P. Murrow,&nbsp;, ,&nbsp;Colby E. Witt,&nbsp;, and ,&nbsp;Ashley E. Ross*,&nbsp;","doi":"10.1021/acschemneuro.5c00554","DOIUrl":"10.1021/acschemneuro.5c00554","url":null,"abstract":"<p >Detection of neurochemicals voltammetrically can be challenging in complex matrices like tissue. Norepinephrine (NE) is a neurotransmitter in the brain and is directly released by the sympathetic nervous system in the periphery. Fast-scan cyclic voltammetry (FSCV) is an electrochemical technique previously used to detect NE from sympathetic neurons in lymphoid tissues. Mesenteric lymph nodes present a unique challenge to FSCV due to their complex tissue matrix, which includes immune cells and neurons. These cells release various neuropeptides, cytokines, and other chemical signaling molecules, which can interfere with FSCV. Notably, Neuropeptide Y (NPY) from sympathetic neurons, and Substance P (SubP) and Calcitonin Gene-Related Peptide (CGRP) from sensory neurons are common peptides that are released locally near NE sites. These peptides are regulated by and interact with NE through complex neuronal circuits, potentially impacting FSCV NE detection. We demonstrate that increasing levels of each peptide alter voltammetric NE detection. We observed that the NE oxidation potential shifts with each peptide in vitro, and NE cyclic voltammograms exhibit unique peak broadening specific to NPY compared to SubP and CGRP, indicating that each peptide affects the carbon fiber microelectrode (CFME) differently. Overall, we show significant convolution of voltammetric NE peaks in the presence of peptides, providing evidence that future developments in materials to reduce protein fouling could significantly improve the robustness and accuracy of NE FSCV detection.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 19","pages":"3851–3860"},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niraparib Demonstrates Therapeutic Potential in Multiple Sclerosis through Inhibition of IL-17A Receptor Interaction and Promotion of Remyelination","authors":"Muge Didem Orhan,&nbsp;, ,&nbsp;Lalehan Oktay,&nbsp;, ,&nbsp;Ayşe Irem Cınar,&nbsp;, ,&nbsp;Aybek Kagan Yesil,&nbsp;, ,&nbsp;Huseyin Tunc,&nbsp;, ,&nbsp;Fatih Eren,&nbsp;, ,&nbsp;Serdar Durdagi,&nbsp;, and ,&nbsp;Timucin Avsar*,&nbsp;","doi":"10.1021/acschemneuro.5c00519","DOIUrl":"10.1021/acschemneuro.5c00519","url":null,"abstract":"<p >IL-17A is a pro-inflammatory cytokine that significantly contributes to the pathogenesis of autoimmune diseases, including multiple sclerosis (MS). Previous studies have suggested that PARP-1 inhibitors can modulate IL-17A-mediated inflammation, prompting the investigation of Niraparib, an FDA-approved PARP-1 inhibitor, as a potential therapeutic agent for MS. In this study, we hypothesized that Niraparib could disrupt the interaction between IL-17A and its receptor, IL-17RA. To evaluate this, we employed a binary quantitative structure−activity relationship (QSAR) model against anti-inflammatory diseases, which indicated Niraparib’s potential efficacy against MS. In silico analyses were conducted to identify key interaction sites and critical amino acid residues involved in the IL-17A/IL-17RA binding. Molecular docking simulations demonstrated Niraparib’s capability to interfere with these interactions. It has demonstrated significant efficacy in inhibiting the interaction between the IL-17A ligand and its receptor via reporter assay. In vivo assessments were performed using a cuprizone-induced demyelination model. Immune profiling revealed modulation of various T cell subsets and B cells, while cytokine analysis indicated a shift in inflammatory responses. Histological evaluations confirmed reduced demyelination and enhanced remyelination in affected brain regions. These findings support Niraparib’s potential as a therapeutic option for MS, warranting further exploration of its mechanisms and clinical relevance.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 19","pages":"3816–3833"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.5c00519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonsurgical Control of Seizure Threshold with Acoustically Targeted Chemogenetics.","authors":"Honghao Li, Shirin Nouraein, Sangsin Lee, Schuyler S Link, Emma K Raisley, Jerzy O Szablowski","doi":"10.1021/acschemneuro.5c00404","DOIUrl":"https://doi.org/10.1021/acschemneuro.5c00404","url":null,"abstract":"<p><p>Many neurological and psychiatric diseases are characterized by pathological neuronal activity. Current treatments involve drugs, surgeries, and implantable devices to modulate or remove the affected region. However, none of these methods can be simultaneously nonsurgical and possess site- and cell type specificity. Here, we apply a nonsurgical neuromodulation approach called Acoustically-Targeted Chemogenetics, or ATAC, to increase the seizure threshold. The ATAC approach used a multipoint focused ultrasound to transiently open the blood-brain barrier of the whole hippocampus (HPC) and transduce pyramidal neurons with engineered G-protein-coupled receptors to inhibit their activity. To express the engineered receptors in the mouse HPC, we used a recently engineered viral vector optimized for ultrasound-based gene delivery to the brain, AAV.FUS.3. In a mouse fluorothyl seizure model, we showed successful gene delivery throughout the HPC, a significant neuronal activity inhibition as evidenced by an increase in seizure threshold. Finally, we benchmarked these effects against a clinically prescribed drug that acts without spatial precision.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulations of Implanted Glutamate Sensor Performance in Three Spatial Dimensions and Time Inform Sensor Design and Data Interpretation","authors":"Mackenzie Clay,&nbsp;Nigel T. Maidment and Harold G. Monbouquette*,&nbsp;","doi":"10.1021/acschemneuro.5c00066","DOIUrl":"10.1021/acschemneuro.5c00066","url":null,"abstract":"<p >Simulations in three dimensions and time provide guidance on implantable, electroenzymatic glutamate sensor design; relative placement in planar sensor arrays; feasibility of sensing synaptic release events; and interpretation of sensor data. Electroenzymatic sensors based on the immobilization of oxidases on microelectrodes have proven valuable for the monitoring of neurotransmitter signaling in deep brain structures; however, the complex extracellular milieu featuring slow diffusive mass transport makes rational sensor design and data interpretation challenging. Simulations show that miniaturization of the disk-shaped device size below a radius of ∼25 μm improves sensitivity, spatial resolution, and the accuracy of glutamate concentration measurements <i>in vivo</i> based on calibration factors determined <i>in vitro</i>. Calculations also show that crosstalk between glutamate sensors in a planar array due to lateral H₂O₂ diffusion is unimportant at micron-scale separation distances, but that the glutamate depletion zone in the vicinity of an individual sensor may limit site spacing to ≳40 μm. Deposition of immobilized glutamate oxidase layers that extend beyond the edge of the underlying microelectrode can improve sensitivity modestly, but H₂O₂ generated by the enzyme at the periphery may not be captured efficiently by the microelectrode, thereby resulting in potentially toxic local H₂O₂ concentrations of ∼25 μM. While simulations predict that detection of glutamate from single-vesicle release events in a synapse would result in current signals that are challenging to detect with conventional equipment, electroenzymatic sensors arranged in planar arrays on biocompatible probes will continue to be a powerful tool for neuroscientists.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 18","pages":"3481–3496"},"PeriodicalIF":3.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Therapies for Alzheimer’s Disease: A New Strategy for Targeted Therapy and Blood–Brain Barrier Delivery","authors":"Xuemei Feng,&nbsp; and ,&nbsp;Hu Wang*,&nbsp;","doi":"10.1021/acschemneuro.5c00484","DOIUrl":"10.1021/acschemneuro.5c00484","url":null,"abstract":"<p >Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuronal loss, with pathological hallmarks including Aβ plaque deposition and tau tangles. At present, the early diagnosis and treatment of AD still face great challenges, such as limited diagnostic methods, difficulty in blood–brain barrier (BBB) penetration, complex disease mechanisms, and lack of highly effective targeted therapies. Antibody drugs have shown broad prospects in the field of AD due to their high specificity, engineering and multifunctional therapeutic potential, include targeted Aβ clearance, tau pathological regulation, imaging probes, and blood biomarkers. In the future, with the development of antibody engineering technologies (such as PROTAC-antibody conjugates and antibody-based gene therapies), the precision diagnosis and treatment of AD is expected to usher in new breakthroughs. This article systematically reviews the latest advances in the treatment and diagnosis of AD and discusses their potential for clinical translation.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 18","pages":"3450–3464"},"PeriodicalIF":3.9,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steering Axon Development: Glial Cell Mechanisms in Drosophila","authors":"Keyao Long,&nbsp;Erqian Huang,&nbsp;Yuhao Yuan,&nbsp;Su Wang* and Menglong Rui*,&nbsp;","doi":"10.1021/acschemneuro.5c00451","DOIUrl":"10.1021/acschemneuro.5c00451","url":null,"abstract":"<p >Glial cells play an indispensable role in the nervous system, providing structural support to neurons and regulating their function and development. Glia support neural network formation and plasticity in axon guidance, synaptic pruning, and neurogenesis. Of note, studies have shown that glial cell dysfunction is closely related to the occurrence of neurological diseases. An in-depth exploration of the multiple roles of glia helps reveal the mechanism of nervous system functioning and provides an important basis for novel therapeutic strategies. <i>Drosophila</i> melanogaster is one of the model organisms for studying glial function because of its relatively simple nervous system, but highly conserved function with mammals. Here, we summarize the studies of <i>Drosophila</i> glial cell roles in axon guidance, pruning, and regeneration, three key processes in axonal development, which aim to understand neuron-glia interactions, as well as provide novel insights into the molecular basis of neurodevelopment and associated neurological disorders.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 18","pages":"3438–3449"},"PeriodicalIF":3.9,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Both Monomer and Oligomer with Fibrinogen Efficiently Suppresses Amyloid Fibril Formation and Cell Toxicity of Amyloid β 1-42","authors":"Naoki Yamamoto*,&nbsp;Keisuke Yuzu,&nbsp;Ken Morishima,&nbsp;Rintaro Inoue,&nbsp;Masaaki Sugiyama,&nbsp;Daisuke Koyama and Eri Chatani,&nbsp;","doi":"10.1021/acschemneuro.5c00562","DOIUrl":"10.1021/acschemneuro.5c00562","url":null,"abstract":"<p >The development of drugs for Alzheimer’s disease, which accounts for over half of all dementia cases, remains challenging. Amyloid β 1-42 (Aβ42) is widely recognized for its deposition in the brains of patients with Alzheimer’s disease. Furthermore, Aβ42-induced cell toxicity likely plays a role in disease onset. Molecular species present in the early stages, such as monomers and oligomers, are appropriate therapeutic targets for suppressing amyloid fibril formation and cell toxicity. In this study, we investigated the effects of bovine fibrinogen (bFg) and human fibrinogen (hFg) since these molecules have been known to exhibit chaperone-like activities. Our findings indicate that bFg exerts a strong inhibitory effect on amyloid fibril formation. Dot blot assays, analytical ultracentrifugation (AUC), and atomic force microscopy (AFM) suggest that bFg interacts with both Aβ42 monomers and oligomers. In contrast, human fibrinogen (hFg), which interacts only with oligomers, exhibits a weaker inhibitory effect on amyloid fibril formation. Moreover, bFg significantly rescued cells from Aβ42-induced toxicity, whereas hFg provided only partial protection. These findings underscore the potential of molecules targeting early stage Aβ42 species as promising candidates for Alzheimer’s disease treatment.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 18","pages":"3623–3630"},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.5c00562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Asaronol, the Neuroactive Component of Acorus tatarinowii: Mitigating Seizures with Minimal Developmental Risk in Dravet Syndrome","authors":"Ying Sun,&nbsp;Yajun Bai*,&nbsp;Bin Li,&nbsp;Peinan Fan,&nbsp;Haiyan Lu,&nbsp;Pu Jia,&nbsp;Ye Zhao,&nbsp;Yujun Bai,&nbsp;Shixiang Wang,&nbsp;Kechun Liu*,&nbsp;Meng Jin*,&nbsp;Tai-Ping Fan* and Xiaohui Zheng*,&nbsp;","doi":"10.1021/acschemneuro.5c00481","DOIUrl":"10.1021/acschemneuro.5c00481","url":null,"abstract":"<p >Developmental epileptic encephalopathies (DEEs), including Dravet syndrome (DS), require antiseizure medications (ASMs) that balance efficacy with developmental safety. There is an urgent clinical need for novel therapeutic agents that combine potent anticonvulsant activity with developmental safety. β-Asarone, an active constituent of <i>Acorus</i> plants, has demonstrated antiepileptic potential, but its toxicities severely limit clinical application. Notably, β-asaronol, a hydroxylated metabolite of β-asarone, may exhibit improved safety; however, its pharmacological properties and therapeutic potential remain systematically unelucidated. To evaluate the developmental safety and antiseizure efficacy of β-asaronol for pediatric refractory epilepsy, developmental toxicity, antiseizure activity, and neuroprotective effects were systematically assessed using zebrafish models (<i>Tg vmat2:GFP</i>, <i>Tg lfabp:EGFP</i>, pentylenetetrazole (PTZ)-induced seizures, and <i>scn1lab</i>^–/– mutants). Electrophysiology, molecular docking, and biomarker analyses elucidated mechanisms. β-Asaronol (5–150 μM) exhibited no significant developmental toxicity in zebrafish, with normal hatching rate, mortality, malformation rate, and no abnormalities in neurotoxicity or hepatotoxicity indicators. Its lethal concentration 50 (LC₅₀) value was 3.5-fold higher than that of the parent compound β-asarone. It prolonged seizure latency, suppressed PTZ-induced hyperactivity (150 μM restoring baseline locomotion), and reduced neuronal apoptosis (lactate dehydrogenase (LDH)/<i>c-fos</i> normalization). In <i>scn1lab</i>^–/– mutants, β-asaronol outperformed stiripentol and cannabidiol, reducing epileptiform discharges by about 93%. Mechanistically, β-asaronol potentiated γ-aminobutyric acid type A (GABA_A) receptor currents (EC₅₀ = 20.8 μM) via benzodiazepine-binding site interactions. β-Asaronol combines superior developmental safety with potent antiseizure efficacy, positioning it as a promising candidate for Dravet syndrome and refractory epilepsy.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 18","pages":"3577–3590"},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of New Blood Immunoassay and Biomarkers for Tau in the Diagnosis of Alzheimer’s Disease","authors":"Xinyu Li,&nbsp;Huimei Zeng,&nbsp;Pradeepraj Durairaj,&nbsp;Weihuan Wen,&nbsp;Tianpeng Li,&nbsp;Yanru Zhao,&nbsp;Yang Liu,&nbsp;Xue Liu,&nbsp;Yida Qiu,&nbsp;Jinming Xing,&nbsp;Fernanda Huang,&nbsp;Li Fu*,&nbsp;Zhicheng Chen* and Hui Cai*,&nbsp;","doi":"10.1021/acschemneuro.5c00301","DOIUrl":"10.1021/acschemneuro.5c00301","url":null,"abstract":"<p >Post-translational modifications, such as truncation facilitated by proteases and phosphorylation mediated by protein kinases, play pivotal roles in Tau protein function and cellular processes. The detection of distinct Tau forms in plasma has garnered significant interest in the scientific and translational communities. We discovered monoclonal antibodies (mAbs) using the hybridoma technique by immunizing mice with different Tau proteins. Enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and Western blot experiments were used to evaluate these mAbs. Following that, we developed immunoassays on ELISA and single-molecule array (Simoa) platforms, respectively. The concentration of Tau fragments in human plasma was detected by Simoa assays to develop novel blood ratio biomarkers. Six mAbs were developed in this study, and on this basis, nine ELISA assays and three Simoa assays were established. The detection limits of Simoa-Assay 1–3 were 0.18, 0.12, and 2.70 pg/mL, respectively. The lower limit of quantification is 0.775, 0.647, and 3.630 pg/mL. The concentrations of three different Tau fragments in plasma were detected by Simoa-Assay 1–3, and the ratios of p-Tau217/t-Tau217 and Tau (1–22)-(187–208)/Tau (1–22)-(210–227) in human plasma are reported for the first time. Our three novel Tau Simoa-assays have the potential to be effective and efficient plasma-based screening tools for Alzheimer’s disease (AD). Furthermore, the new ratios p-Tau217/t-Tau217 and Tau (1–22)-(187–208)/Tau (1–22)-(210–227) may be potential novel AD plasma biomarkers.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 18","pages":"3527–3540"},"PeriodicalIF":3.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}