{"title":"Evaluation of 6 monoclonal antibodies against Ser129-phosphorylated α-synuclein: Critical role of proteinase K antigen retrieval and superior sensitivity of the D1R1R clone in human skin biopsies.","authors":"Cecilia Delprete, Alex Incensi, Alessandro Furia, Riccardo Bari, Rocco Liguori, Vincenzo Donadio","doi":"10.1093/jnen/nlaf036","DOIUrl":"https://doi.org/10.1093/jnen/nlaf036","url":null,"abstract":"<p><p>α-Synuclein is an essential component of synucleinopathies including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy (MSA). Misfolded-α-synuclein inclusions that contain high levels of Serine-129 phosphorylated (pS129-α-syn) are key diagnostic markers. Skin biopsies are a promising peripheral tissue for in vivo detection of aggregates using immunofluorescence staining. Several primary antibodies target pS129-α-syn but their diagnostic reliability remains uncertain. Common practice relies on clones EP1536Y and 81A without antigen retrieval; however, recent findings have underscored the need to validate additional methodologies and alternative clones. We compared the diagnostic accuracy of the standard protocol, alongside formic acid and proteinase K (PK) antigen retrieval to evaluate 4 additional monoclonal antibodies (J18, BBF19, pSyn#64, and D1R1R) in a cohort of 43 confirmed synucleinopathy patients (7 with MSA) and 33 healthy controls. The results showed that PK increased the detection rates for EP1536Y, 81A, and D1R1R, with D1R1R outperforming the others in sensitivity. J18, BBF19, and pSyn#64 exhibited insufficient specificity, limiting their clinical applicability. The improved accuracy with PK treatment and the promising performance of D1R1R mark critical advancements for reliable diagnosis, highlighting the importance of optimizing protocols and validating antibodies for dependable detection of pathological aggregates in skin biopsies.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967894","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":"Adequate capture of spatial heterogeneity of Ki-67 proliferative index in meningiomas requires multiple tissue sections.","authors":"Ugochukwu Ugwuowo, Bethany Faust, Haiming Tang, Marcello DiStasio","doi":"10.1093/jnen/nlaf043","DOIUrl":"https://doi.org/10.1093/jnen/nlaf043","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031448","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":"Correction to: Comorbidities in early-onset sporadic versus presenilin-1 mutation-associated Alzheimer disease dementia: Evidence for dependency on Alzheimer disease neuropathological changes.","authors":"","doi":"10.1093/jnen/nlaf030","DOIUrl":"https://doi.org/10.1093/jnen/nlaf030","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997788","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}
Angelique D Gonzalez, Yannick N Wadop, Benjamin Danner, Kyra M Clarke, Matthew B Dopler, Ali Ghaseminejad-Bandpey, Sahana Babu, Julie Parker-Garza, Cole Corbett, Mohammad Alhneif, Mallory Keating, Kevin F Bieniek, Gladys E Maestre, Sudha Seshadri, Shahroo Etemadmoghadam, Bernard Fongang, Margaret E Flanagan
{"title":"Digital pathology in tau research: A comparison of QuPath and HALO.","authors":"Angelique D Gonzalez, Yannick N Wadop, Benjamin Danner, Kyra M Clarke, Matthew B Dopler, Ali Ghaseminejad-Bandpey, Sahana Babu, Julie Parker-Garza, Cole Corbett, Mohammad Alhneif, Mallory Keating, Kevin F Bieniek, Gladys E Maestre, Sudha Seshadri, Shahroo Etemadmoghadam, Bernard Fongang, Margaret E Flanagan","doi":"10.1093/jnen/nlaf026","DOIUrl":"https://doi.org/10.1093/jnen/nlaf026","url":null,"abstract":"<p><p>The application of digital pathology tools has expanded in recent years, but non-neoplastic human brain tissue presents unique challenges due to its complexity. This study evaluated HALO and QuPath tau quantification performance in the hippocampus and mid-frontal gyrus across various tauopathies. Percent positivity emerged as the most reliable measure, showing strong correlations with Braak stages and CERAD scores, outperforming object and optical densities. QuPath demonstrated superior correlations with Braak stages, while HALO excelled in aligning with CERAD scoring. However, HALO's optical density was less consistent. Paired t-tests revealed significant differences in object and optical densities between platforms, though percent positivity was consistent across both. QuPath's threshold-based object density showed similar agreement with manual counts compared to HALO's AI-dependent approach (all ρ > 0.70). Reanalysis of QuPath further improved its agreement with manual measurements and correlations with Braak and CERAD scores (all ρ > 0.70). HALO offers a user-friendly interface and excels in certain metrics but is hindered by frequent software malfunctions and more limited flexibility. In contrast, QuPath's customizable workflows and superior performance in Braak staging make it more suitable for advanced and larger-scale analyses. Overall, our study highlights the strengths and limitations of these platforms, helping guide their application in neuropathology.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014920","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}
Ramada R Khaswaneh, Ejlal Abu-El-Rub, Ayman Alzu'bi, Rawan Almazari, Amneh Alrabie, Fatimah A Almahasneh, Amani Kasasbeh, Heba F Ai-Jariri, Ayman Mustafa
{"title":"Combining dopamine and vitamin E enhances the differentiation to cholinergic neurons of mesenchymal stem cells.","authors":"Ramada R Khaswaneh, Ejlal Abu-El-Rub, Ayman Alzu'bi, Rawan Almazari, Amneh Alrabie, Fatimah A Almahasneh, Amani Kasasbeh, Heba F Ai-Jariri, Ayman Mustafa","doi":"10.1093/jnen/nlaf025","DOIUrl":"https://doi.org/10.1093/jnen/nlaf025","url":null,"abstract":"<p><p>Recent research indicates that mesenchymal stem cells (MSCs) can transdifferentiate into neuron-like cells under specific conditions, offering promise for neuronal regeneration. However, challenges remain in optimizing differentiation protocols to generate specific neuron types. This study explores the impact of supplementing neuronal induction media with dopamine and vitamin E to guide MSCs toward specific neuronal subtypes. Human adipose-MSCs were utilized to investigate neuronal differentiation. The cells were cultured in induction media supplemented with 2 concentrations of dopamine (2.5 and 5 µM) and vitamin E (12.5 and 25 µM). Immunostaining and western blot analysis were employed to assess the sequential expression of neuronal markers associated with various stages of maturation and development. These markers included Nestin, MAP2, NeuN, TBR1, SATB2, DAT, DBH, and CHAT. The results demonstrate, for the first time, that supplementing neuronal induction media with dopamine and vitamin E significantly enhances and accelerates the differentiation of MSCs into neuronal cells. Furthermore, the findings suggest that the induced cells are predominantly reprogrammed toward a cholinergic neuronal lineage. For MSCs, our study reveals that the addition of dopamine and vitamin E reprograms MSCs mainly toward cholinergic neurons, suggesting promising approaches for treating neurodegenerative disorders.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023273","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}
Phuong Nguyen, Raquel T Yokoda, Quazi Hossain, Joshua B Bederson, Timothy E Richardson
{"title":"Solitary fibrous tumor-meningioma collision tumor with 18 years of follow-up.","authors":"Phuong Nguyen, Raquel T Yokoda, Quazi Hossain, Joshua B Bederson, Timothy E Richardson","doi":"10.1093/jnen/nlaf037","DOIUrl":"https://doi.org/10.1093/jnen/nlaf037","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026295","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":"Correction to: PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury.","authors":"","doi":"10.1093/jnen/nlaf027","DOIUrl":"https://doi.org/10.1093/jnen/nlaf027","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811644","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}
Christie G Turin, Timothy H Ung, B K Kleinschmidt-DeMasters
{"title":"TBX19/SF1 co-expressing pituitary neuroendocrine tumor/pituitary adenomas add to the lineage infidelity.","authors":"Christie G Turin, Timothy H Ung, B K Kleinschmidt-DeMasters","doi":"10.1093/jnen/nlaf028","DOIUrl":"https://doi.org/10.1093/jnen/nlaf028","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803470","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}
Felipe J S Jones, Emily Ling-Lin Pai, Rogan Magee, Kelly Boylan, Vivian Chioma, Jessica Little, Daniel Yoshor, Jose L Pascual, Amir Banihashemi, Sashank Prasad, Edward B Lee, Jennifer Orthmann-Murphy
{"title":"Consecutive brain biopsies illustrate the histological evolution of acute hemorrhagic leukoencephalitis.","authors":"Felipe J S Jones, Emily Ling-Lin Pai, Rogan Magee, Kelly Boylan, Vivian Chioma, Jessica Little, Daniel Yoshor, Jose L Pascual, Amir Banihashemi, Sashank Prasad, Edward B Lee, Jennifer Orthmann-Murphy","doi":"10.1093/jnen/nlaf019","DOIUrl":"https://doi.org/10.1093/jnen/nlaf019","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780372","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}