Journal of Neural Transmission最新文献_第2页

A new vision of the role of the cerebellum in pain processing. 对小脑在疼痛处理中的作用的新认识。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-04-01 Epub Date: 2025-01-11 DOI: 10.1007/s00702-024-02872-1

José Mário Prati, Anna Carolyna Gianlorenço

{"title":"A new vision of the role of the cerebellum in pain processing.","authors":"José Mário Prati, Anna Carolyna Gianlorenço","doi":"10.1007/s00702-024-02872-1","DOIUrl":"10.1007/s00702-024-02872-1","url":null,"abstract":"The cerebellum is a structure in the suprasegmental nervous system classically known for its involvement in motor functions such as motor planning, coordination, and motor learning. However, with scientific advances, other functions of the cerebellum, such as cognitive, emotional, and autonomic processing, have been discovered. Currently, there is a body of evidence demonstrating the involvement of the cerebellum in nociception and pain processing. The aim of this review is to present the current literature on the anatomical, physiological, and functional aspects of the cerebellum in pain processing and suggest functional mechanisms of pain processing based on the cerebellum and its connections with other brain structures. To achieve this, searches were conducted in databases to identify relevant studies on the topic. Studies with relevant data and information were collected and summarized. Current literature demonstrates that the cerebellum receives nociceptive afferents from different pathways and exhibits activity in different regions including the vermis, hemispheres, and deep cerebellar nuclei in pain processing. Through its connections with different brain regions, it is possible that the cerebellum participates in the multidimensional processing of pain, which may make it a potential therapeutic target for pain treatment.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"537-546"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alzheimer mimicry: LATE and PART. 阿尔茨海默症：晚期和部分。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-31 DOI: 10.1007/s00702-025-02916-0

Nenad Bogdanovic, Una Smailovic, Vesna Jelic

{"title":"Alzheimer mimicry: LATE and PART.","authors":"Nenad Bogdanovic, Una Smailovic, Vesna Jelic","doi":"10.1007/s00702-025-02916-0","DOIUrl":"https://doi.org/10.1007/s00702-025-02916-0","url":null,"abstract":"Alzheimer's disease (AD) is the main cause of dementia and accounts for 60% of dementia syndromes in people older than 75 years. The correct classification of AD and non-AD cases is mandatory to study disease mechanisms or new treatment possibilities. A typical clinical picture of AD consists of a progressive cognitive decline, with primary memory impairment. Structural, functional, and molecular brain imaging, along with CSF biomarkers of amyloid pathology, neurodegeneration, and the presence of a vulnerability-associated APOE genotype, support the diagnosis of AD. Use of biomarkers have led to the identification of individuals with mild cognitive impairment who are amyloid-negative addressing a conceptually separate clinical entity named suspected non-Alzheimer disease pathophysiology (SNAP). Clinical presentation and progression of SNAP can mimic AD which makes the final diagnosis and possible treatment uncertain in up to 30% of cases in clinical centers that are not using biomarkers. These non-AD pathologies are common with advancing age both in cognitively impaired and clinically normal elderly people and include Argyrophilic Grain Disease (ARG), Tangle Predominant Dementia and TDP-43 proteinopathy. The terms Primary age-related tauopathy (PART) and Limbic-dominant TDP-43 age-related encephalopathy (LATE) have been proposed as the most common and useful biological and emerging clinical construct to describe this phenomenon in > 80 years old individuals. Current evidence underlines the limitations of existing diagnostic tools, which remain inadequate for fully capturing the complexities of these conditions. Addressing these diagnostic ambiguities is crucial for assigning accurate diagnoses, reducing frequent misdiagnoses of AD, and implementing appropriate therapeutic strategies for elderly patients with mild cognitive impairment and dementia.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative efficacy of Mucuna pruriens and conventional levodopa in Parkinson's disease: a randomized controlled trial on pharmacokinetics and clinical perspectives from Asia. 麝香草与常规左旋多巴治疗帕金森病的比较疗效：一项来自亚洲的药代动力学和临床观点的随机对照试验

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-26 DOI: 10.1007/s00702-025-02914-2

Thanatat Boonmongkol, Onanong Phokaewvarangkul, Sornkanok Vimolmangkang, Thitima Wattanavijitkul, Virunya Komenkul, Roongroj Bhidayasiri

{"title":"Comparative efficacy of Mucuna pruriens and conventional levodopa in Parkinson's disease: a randomized controlled trial on pharmacokinetics and clinical perspectives from Asia.","authors":"Thanatat Boonmongkol, Onanong Phokaewvarangkul, Sornkanok Vimolmangkang, Thitima Wattanavijitkul, Virunya Komenkul, Roongroj Bhidayasiri","doi":"10.1007/s00702-025-02914-2","DOIUrl":"https://doi.org/10.1007/s00702-025-02914-2","url":null,"abstract":"Levodopa remains central to Parkinson's disease (PD) treatment, but long-term use can cause motor complications, highlighting the need for additional therapies. Mucuna pruriens (MP), a natural source of levodopa, shows potential in managing these complications. Further research is needed to compare its pharmacokinetics (PK) and clinical outcomes with traditional levodopa formulations. This randomised, single-blind, crossover trial compared the PK, clinical outcomes, and safety of MP powder against levodopa/benserazide dispersible tablets (Levodopa DT) in PD patients with motor complications. Twelve participants were recruited to receive either 30 g of MP powder or two 100/25 levodopa DT in separate sessions with a two-week washout between sessions. Key PK parameters (AUC, Cmax, Tmax, and t½) were measured. Clinical assessments used standard rating scales and adverse events were recorded. Data from 11 participants were analysed after one withdrawal. MP powder demonstrated significantly higher overall drug exposure, with a geometric mean AUC0-∞ of 12,424.81 compared to 7981.69 ng·h/mL for levodopa DT. The geometric mean ratio was 155.67% (90% CI 134.59-180.04), exceeding the bioequivalence acceptance range of 80-125%. However, the two treatments exhibited similar Tmax and t₁/₂ values, indicating comparable rates of absorption and elimination. Clinically, MP provided a longer ON state without dyskinesia-232.2 min versus 161.8 min for levodopa DT (p = 0.01). Mild and transient adverse events, such as nausea and dizziness, were more frequently associated with MP. MP offers superior drug exposure and extends the ON state without increasing dyskinesia, positioning it as a promising alternative to synthetic levodopa for managing motor symptoms. These findings support MP's potential role in alleviating motor complications in PD treatment.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: The centenarian blueprint: lessons in defying Parkinson's disease. 更正：百岁老人的蓝图：对抗帕金森氏症的教训。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-25 DOI: 10.1007/s00702-025-02900-8

Roongroj Bhidayasiri, Ikuko Aiba, Masahiro Nomoto

引用次数: 0

Investigation of the voice handicaps in Parkinson's disease and determination of the clinical correlates. 帕金森病嗓音障碍的调查及临床相关因素的确定。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-24 DOI: 10.1007/s00702-025-02910-6

Halil Onder, Meral Oksuz, Selcuk Comoglu

{"title":"Investigation of the voice handicaps in Parkinson's disease and determination of the clinical correlates.","authors":"Halil Onder, Meral Oksuz, Selcuk Comoglu","doi":"10.1007/s00702-025-02910-6","DOIUrl":"https://doi.org/10.1007/s00702-025-02910-6","url":null,"abstract":"Speech impairment is a common and disabling symptom of Parkinson's disease (PD). We aimed to reveal the motor, nonmotor, and other clinical factors that might be associated with voice disturbances in PD. Remarkably, we aimed to present a possible specific clinical phenotype more prone to display speech disturbances. We included all the patients with PD who visited our movement disorders clinic between March 2023 and March 2024 and whose information regarding the clinical features and scale results was fully available. In addition to detailed demographic data, comprehensive clinical assessments were performed. We included 232 PD patients with a mean age of 64.4 ± 10.5 y (F/M = 145/87). The median disease duration was 4 y. The comparative analyses of the patients with and without voice handicaps (VH) revealed that patients with VH had higher disease duration and LED. They got higher scores in all the clinical scales, including MDS-UPDRS 1, 2, 3, 4, FOGQ, FES-I, HAM-A, and HDRS revealing a more severe disease stage However, multiple linear regression models revealed only the MDS-UPDRS 4 score, HAM-A score, and MDS-UPDRS-3 (on) score [- 10,658 + 2297*MDS-UPDRS-4 + 0949*HAI + 0549*MDS-UPDRS-3 (on)] as predictors of VHI. Our results support increasing speech problems with higher motor stage, and motor complication score. Besides, we also draw attention to anxiety, which is associated with speech problems in the general community, but only in an experimental study of PD pathology.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep brain stimulation in progressive supranuclear palsy: a dead-end story? A narrative review. 深部脑刺激治疗进行性核上性麻痹：一个没有出路的故事？叙述性评论

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-24 DOI: 10.1007/s00702-025-02904-4

Gabriele Bellini, Giulia Di Rauso, Lorenzo Fontanelli, Elena Benevento, Lucrezia Becattini, Daniela Frosini, Roberto Ceravolo, Eleonora Del Prete

{"title":"Deep brain stimulation in progressive supranuclear palsy: a dead-end story? A narrative review.","authors":"Gabriele Bellini, Giulia Di Rauso, Lorenzo Fontanelli, Elena Benevento, Lucrezia Becattini, Daniela Frosini, Roberto Ceravolo, Eleonora Del Prete","doi":"10.1007/s00702-025-02904-4","DOIUrl":"https://doi.org/10.1007/s00702-025-02904-4","url":null,"abstract":"Progressive supranuclear palsy (PSP) is a rare, debilitating neurodegenerative disorder that significantly impairs both motor and cognitive functions. Current pharmacological treatments offer only transient symptomatic relief, driving interest in the past in alternative therapeutic strategies such as deep brain stimulation. Deep brain stimulation (DBS), known for its success in treating motor symptoms of Parkinson's disease, has been explored as a possible symptomatic treatment for PSP, considering the pedunculopontine nucleus (PPN), involved in motor control and postural stability, as a promising target for deep brain stimulation in PSP. However, its complex anatomy and the clinical variability of PSP complicate the prediction and generalization of the effectiveness of DBS. The present review examines the existing studies in the literature about DBS in PSP patients. Some studies highlighted modest benefits in motor symptoms, while others reported variable outcomes and inherent risks of the procedure. Generally, patients with a parkinsonism predominant phenotype have shown some subjective or clinical improvements in gait and balance when subjected to low-frequency stimulation. While DBS of the PPN holds promise for ameliorating gait and balance of PSP, current evidence does not yet establish clear criteria for ideal candidates, nor does it provide overwhelmingly supportive results in favor of PPN-DBS in PSP patients. Without any further systematic study is not possible to define accurate candidate selection parameters and understand long-term outcomes and safety profiles.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic innovations for the symptomatic treatment of Parkinson's disease: focus on technology-based therapies. 帕金森病对症治疗的治疗创新：关注基于技术的疗法。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-22 DOI: 10.1007/s00702-025-02915-1

Jeryl Ritzi T Yu, Avery Kundrick, Enrique C Panganiban, Michelle Ann Sy, Saar Anis, Hubert H Fernandez

{"title":"Therapeutic innovations for the symptomatic treatment of Parkinson's disease: focus on technology-based therapies.","authors":"Jeryl Ritzi T Yu, Avery Kundrick, Enrique C Panganiban, Michelle Ann Sy, Saar Anis, Hubert H Fernandez","doi":"10.1007/s00702-025-02915-1","DOIUrl":"https://doi.org/10.1007/s00702-025-02915-1","url":null,"abstract":"As Parkinson's disease (PD) progresses, patients experience motor fluctuations, which may manifest as motor and/or non-motor wearing off symptoms, delayed \"ON\" time, and/or levodopa-related dyskinesia. Deep brain stimulation (DBS) is an effective therapy but may not be suitable for all patients due to factors such as premorbid conditions age, or accessibility. We review technology-based therapeutic innovations for PD: infusion therapies and novel non-invasive neuromodulation methods using the following databases: PubMed, Cochrane, and Science Direct. Infusion therapies such as percutaneous (LCIG, LECIG) and subcutaneous options (ND0612, foslevodopa-foscarbidopa, CSAI) demonstrate significant benefits in reducing OFF time and enhancing ON time without troublesome dyskinesias. However, vigilance is required for procedural and skin adverse events. Neuromodulation approaches such as auricular, vagus nerve, and galvanic vestibular stimulation, as well as whole-body vibration, showed promising benefits in freezing of gait (FOG) and tremor. Infusion and non-invasive neuromodulation therapies provide additional treatment options for patients with refractory motor and non-motor symptoms and may be an alternative for those who experience limitations of traditional dopaminergic therapies and are not candidates for neurosurgical interventions.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real-world experience with continuous subcutaneous foslevodopa/foscarbidopa infusion: insights and recommendations. 持续皮下注射foslevodopa/foscarbidopa的实际经验：见解和建议。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-22 DOI: 10.1007/s00702-025-02911-5

Thomas Koeglsperger, Emir Berberovic, Christian Dresel, Sebastian Haferkamp, Jan Kassubek, Rahel Müller, Christian Oehlwein, Sebastian Paus, Peter Paul Urban

{"title":"Real-world experience with continuous subcutaneous foslevodopa/foscarbidopa infusion: insights and recommendations.","authors":"Thomas Koeglsperger, Emir Berberovic, Christian Dresel, Sebastian Haferkamp, Jan Kassubek, Rahel Müller, Christian Oehlwein, Sebastian Paus, Peter Paul Urban","doi":"10.1007/s00702-025-02911-5","DOIUrl":"https://doi.org/10.1007/s00702-025-02911-5","url":null,"abstract":"Traditional advanced therapies in Parkinson's disease (PD) with motor fluctuations and dyskinesias like continuous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel (LCIG), levodopa-carbidopa entacapone intestinal gel (LECIG), or deep brain stimulation (DBS) have played a central role in managing therapy-related complications. Recently, continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) has emerged as a novel therapeutic option. This manuscript provides insights from one year of real-world experience with CSFLI, addressing critical questions that clinicians face when selecting the most appropriate therapy for advanced PD. Our discussion centers on key considerations for patient selection, exploring which individuals may benefit more from CSFLI compared to other device-aided therapies. We highlight CSFLI's advantages in flexibility and ease of use but also consider limitations, particularly its side effects, such as skin-related issues. Recommendations are presented on how to prevent and manage these adverse effects to maximize patient compliance and therapeutic success. Additionally, the paper examines strategies for optimizing concurrent oral medications when combined with CSFLI, providing guidance on balancing pump infusion with necessary adjunctive oral treatments.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abnormal iron metabolism in the zona incerta in Parkinson's disease mice. 帕金森病小鼠不动带铁代谢异常。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-22 DOI: 10.1007/s00702-025-02913-3

Minxia Xiu, Yanhong Liu, Zhaobo Wang, Jing Zhang, Yaying Shi, Junxia Xie, Limin Shi

{"title":"Abnormal iron metabolism in the zona incerta in Parkinson's disease mice.","authors":"Minxia Xiu, Yanhong Liu, Zhaobo Wang, Jing Zhang, Yaying Shi, Junxia Xie, Limin Shi","doi":"10.1007/s00702-025-02913-3","DOIUrl":"https://doi.org/10.1007/s00702-025-02913-3","url":null,"abstract":"Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and abnormal iron metabolism. While most of the current studies have focused on nigral iron deposition, there is still limited research into the role of iron in other brain regions. The zona incerta (ZI) is a heterogeneous subthalamic region and has extensive connections with the basal ganglia nucleus. Clinically, the ZI has been recognized as a new therapeutic target for PD. Deep brain stimulation of the ZI has been reported to relieve motor symptoms and experimental heat pain in patients with PD. The aim of the present study is to evaluate changes in iron levels in the ZI. Two neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), were used to prepare PD mice. By immunostaining, we first measured the success of MPTP or 6-OHDA injury. We found that the expressions of tyrosine hydroxylase were decreased after MPTP or 6-OHDA treatment. Secondly, we observed the changes of iron metabolism using Perls' iron staining and western blots. Our results showed that the numbers of iron-positive cells were significantly increased in the SN and ZI of MPTP/6-OHDA-treated mice. Moreover, the expression levels of ferritin and divalent metal transporter 1 (DMT1) in the ZI were also increased in the PD group. Glutathione peroxidase 4 (GPX4), a marker of ferroptosis, was also detected. Western blots revealed that MPTP significantly down-regulated the level of GPX4 in the ZI. As glial cells activation and neuroinflammation play important roles in the ion deposition, we finally investigated the microglial and astrocyte activation and inflammatory factors. These results suggested increased iron levels and inflammation may be present in the ZI in PD mice.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical characterization of Tau protein changes and amyloid dynamics in a novel non-transgenic rat model of tauopathy. 新型非转基因大鼠Tau病模型中Tau蛋白变化和淀粉样蛋白动力学的生化表征。

IF 3.2 4区医学

Journal of Neural Transmission Pub Date : 2025-03-17 DOI: 10.1007/s00702-025-02909-z

Lea Langer Horvat, Ena Španić Popovački, Mirjana Babić Leko, Klara Zubčić, Maja Mustapić, Patrick R Hof, Goran Šimić

{"title":"Biochemical characterization of Tau protein changes and amyloid dynamics in a novel non-transgenic rat model of tauopathy.","authors":"Lea Langer Horvat, Ena Španić Popovački, Mirjana Babić Leko, Klara Zubčić, Maja Mustapić, Patrick R Hof, Goran Šimić","doi":"10.1007/s00702-025-02909-z","DOIUrl":"https://doi.org/10.1007/s00702-025-02909-z","url":null,"abstract":"In this study, we further characterized a non-transgenic model of tauopathy by examining tau protein changes using ELISA and Western blot upon inoculation of human tau oligomers (TO) and human tau synthetic pre-formed fibrils (TF) into the medial entorhinal cortex of Wistar rats. Our analyses showed that inoculation with TO did not significantly alter the ratio of phosphorylated tau at AT8 epitopes (pSer202/pThr205) to total tau protein in the hippocampus and entorhinal cortex, but only resulted in a decrease of phosphorylation at AT100 epitopes (pThr212/pSer214). As we previously observed an increase in AT8 immunostaining in both regions, this suggests method-dependent conformational alterations. In contrast, eleven months after inoculation, TF caused significant AT8 and PHF-1 (pSer396/pSer404) epitope-specific changes in tau phosphorylation in the hippocampus, but not in the entorhinal cortex, reflecting a more advanced stage of Alzheimer's disease (AD)-like changes compared to TO. Importantly, amyloid plaques appeared as early as four months post-inoculation with TO, preceding significant phosphorylation changes of tau, thus indicating that amyloid probably facilitates early tau seeding and spreading. This was corroborated by the observed dynamic changes in Aβ1-42 levels in cerebrospinal fluid, with initial decreases followed by increases, similar to patterns seen in transgenic mouse models of AD and in AD patients. Altogether, these findings lead us to conclude that changes in tau protein induce amyloid changes and vice versa, which is actually what defines AD as a unique neurodegenerative disease.","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0