Journal of Neuropathology and Experimental Neurology最新文献_第7页

Magnetic susceptibility matched fluid for neuroimaging assessed in histology and stereology: A pilot study. 在组织学和体视学中评估神经成像的磁化率匹配流体：一项初步研究。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlaf165

Emma W Rosenblum, Daigo Takeuchi, Smriti Chadha, Nathaniel D Mercaldo, Emily M Williams, Jessica Roy, Jerome L Ackerman, Jean C Augustinack

{"title":"Magnetic susceptibility matched fluid for neuroimaging assessed in histology and stereology: A pilot study.","authors":"Emma W Rosenblum, Daigo Takeuchi, Smriti Chadha, Nathaniel D Mercaldo, Emily M Williams, Jessica Roy, Jerome L Ackerman, Jean C Augustinack","doi":"10.1093/jnen/nlaf165","DOIUrl":"10.1093/jnen/nlaf165","url":null,"abstract":"Ex vivo MRI allows for ultra-high resolution image acquisition and valuable validation when combined with histology. Postmortem brain samples may undergo long scan times without motion artifacts. Perfluoropolyethers such as Fomblin have become a popular choice of immersion liquid for their \"proton free\" appearance and their ability to eliminate susceptibility artifacts from the tissue-air interface but the effect of Fomblin on downstream histology experiments has not been previously studied. We exposed rat brain samples to Fomblin (n = 4) versus a control group (n = 4). Samples underwent histochemical (Nissl) and immunohistochemical staining for NeuN to assess neurons and background staining. The optical fractionator method was applied to assess total neuron counts and tissue thickness. Samples from the Fomblin group showed consistent NeuN and Nissl staining when compared to the control group. The staining color, evenness, and neuron visualization appeared unaffected with no background staining. The total neuron counts, and tissue thickness showed only slight differences in absolute numbers between groups with insufficient evidence to conclude the distribution of total neuron number or tissue thickness differed by group. These data suggest that Fomblin may not negatively impact histochemical staining, immunohistochemistry, or total neuron counts in the short term.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"747-755"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998353","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}

引用次数: 0

Identification of diagnostic biomarkers for relapsing-remitting multiple sclerosis in plasma by mass spectrometry-based proteomics. 以质谱为基础的蛋白质组学鉴定血浆中复发缓解型多发性硬化的诊断性生物标志物。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlaf145

Víctor M García-Silva, Eduardo Chicano-Galvez, María Isabel García-Sánchez, Ángela Peralbo-Molina, María Hernández-Valladares

{"title":"Identification of diagnostic biomarkers for relapsing-remitting multiple sclerosis in plasma by mass spectrometry-based proteomics.","authors":"Víctor M García-Silva, Eduardo Chicano-Galvez, María Isabel García-Sánchez, Ángela Peralbo-Molina, María Hernández-Valladares","doi":"10.1093/jnen/nlaf145","DOIUrl":"10.1093/jnen/nlaf145","url":null,"abstract":"In the absence of molecular biomarkers, the current diagnosis of multiple sclerosis is based on clinical assessment, neuroimaging, and detection of oligoclonal bands in cerebrospinal fluid. Early and rapid diagnosis using patient samples obtained by non-invasive methods would be a major advance in clinical management. We tested 5 different methods for preparation of the plasma proteome for liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. These were as follows: (1) single-pot, solid-phase-enhanced sample preparation (SP3), (2) iST and (3) ENRICH-iST of raw plasma, (4) SP3 of highly abundant-proteins depleted plasma (DEPL-SP3), and (5) SP3 of plasma extracellular vesicles (EV-SP3). DEPL-SP3 and EV-SP3 sample preparation workflows yielded the highest numbers of quantified plasma proteins. Using both methods, we analyzed the plasma proteome of 15 relapsing-remitting multiple sclerosis (RRMS) patients and 5 healthy controls. We found 54 and 35 regulated plasma proteins with DEPL-SP3 and EV-SP3 workflows, respectively. Among them, von Villebrand factor (VWF) was identified as a potential RRMS diagnostic biomarker. The use of sample preparation workflows for LC-MS/MS analysis that describe both the soluble and EV plasma proteomes might increase the likelihood of identifying new and robust RRMS biomarkers.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"768-776"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804586","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}

引用次数: 0

Astrocyte-vascular interactions are disturbed in cerebral white matter of adult-onset neuronal intranuclear inclusion disease. 星形细胞-血管相互作用在成人发病的神经元核内包涵病的脑白质中受到干扰。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-07-01 DOI: 10.1093/jnen/nlag002

Daisuke Yoshii, Takashi Ayaki, Takafumi Wada, Tomohisa Okada, Atsushi Shima, Yuta Terada, Shohei Yamada, Kaoru Seiriki, Atsushi Kasai, Hitoshi Hashimoto, Atsushi Umemura, Tomoko Oeda, Keiko Toyooka, Nobuhisa Okada, Harutoshi Fujimura, Takakuni Maki, Nobukatsu Sawamoto, Takashi Hanakawa, Akihiko Ozaki, Toru Yamamoto, Yoshimi Miyagi, Hideto Senzaki, Ryosuke Takahashi, Riki Matsumoto

{"title":"Astrocyte-vascular interactions are disturbed in cerebral white matter of adult-onset neuronal intranuclear inclusion disease.","authors":"Daisuke Yoshii, Takashi Ayaki, Takafumi Wada, Tomohisa Okada, Atsushi Shima, Yuta Terada, Shohei Yamada, Kaoru Seiriki, Atsushi Kasai, Hitoshi Hashimoto, Atsushi Umemura, Tomoko Oeda, Keiko Toyooka, Nobuhisa Okada, Harutoshi Fujimura, Takakuni Maki, Nobukatsu Sawamoto, Takashi Hanakawa, Akihiko Ozaki, Toru Yamamoto, Yoshimi Miyagi, Hideto Senzaki, Ryosuke Takahashi, Riki Matsumoto","doi":"10.1093/jnen/nlag002","DOIUrl":"10.1093/jnen/nlag002","url":null,"abstract":"Adult-onset neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease that is pathologically characterized by eosinophilic hyaline intranuclear inclusions, mainly in astrocytes, and cerebral white matter degeneration. However, the pathogenesis underlying these neuropathological findings remains unclear. We previously reported an autopsy case of adult-onset NIID with characteristic perivascular findings. In that case, the perivascular areas were preserved despite cerebral white matter damage but dense glial fibrillary acidic protein-immunoreactive astrocytic processes were observed around the blood vessels. The present study examined 2 additional cases and confirmed that the above findings were common in patients with adult-onset NIID. To investigate the underlying pathophysiology behind these findings, immunohistochemistry was performed for proteins located in the astrocytic end-feet. In the cerebral white matter of all NIID cases, there was an altered distribution of aquaporin 4 (AQP4) with increased AQP4-immunopositive areas compared to control cases. These results suggest that the interaction between astrocytes and blood vessels, particularly involving water homeostasis, may be impaired in the cerebral white matter of patients with NIID.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"736-746"},"PeriodicalIF":3.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132181","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}

引用次数: 0

An unusual extra-axial supratentorial presentation of atypical teratoid/rhabdoid tumor in a child. 儿童不典型畸胎瘤/横纹肌样瘤的不寻常轴外幕上表现。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-06-27 DOI: 10.1093/jnen/nlag068

Vich Yindeedej, Putch Phairintr, Ploy Wisetsathon, Thitirat Lokhoonsombut, Pacharapan Surapolchai

引用次数: 0

Novel YWHAE-NTRK3 fusion in a pediatric glioma. 新型YWHAE-NTRK3融合治疗小儿胶质瘤。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-06-26 DOI: 10.1093/jnen/nlag065

Anina Fiocchi, Elisabeth J Rushing, Simone Brandt, Jonas Kloepper, Kiriaki Kollia, René L Bernays

引用次数: 0

Comprehensive clinicomolecular characterization of a methylation-defined supratentorial high-grade astrocytoma with piloid features in a young adult with confirmed germline NF1 mutation. 一名确认种系NF1突变的年轻成人中甲基化定义的具有毛样特征的幕上高度星形细胞瘤的综合临床分子特征。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-06-26 DOI: 10.1093/jnen/nlag067

Matthieu Pallandre, Maroa Dridi, Wafa Bouleftour, Fabien Forest, Carole Ramirez

引用次数: 0

Association of CDKN2A/B and MTAP deletions in adult-type diffuse gliomas. CDKN2A/B和MTAP缺失在成人型弥漫性胶质瘤中的关联

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-06-01 DOI: 10.1093/jnen/nlag007

Blake A Ebner, Cristiane M Ida, Thomas M Kollmeyer, Robert B Jenkins, Cinthya J Zepeda Mendoza, Caterina Giannini, Jorge A Trejo-Lopez, Aditya Raghunathan

{"title":"Association of CDKN2A/B and MTAP deletions in adult-type diffuse gliomas.","authors":"Blake A Ebner, Cristiane M Ida, Thomas M Kollmeyer, Robert B Jenkins, Cinthya J Zepeda Mendoza, Caterina Giannini, Jorge A Trejo-Lopez, Aditya Raghunathan","doi":"10.1093/jnen/nlag007","DOIUrl":"10.1093/jnen/nlag007","url":null,"abstract":"In adult-type diffuse gliomas CDKN2A and/or CDKN2B (CDKN2A/B) deletions often co-occur with deletion of MTAP, suggesting that MTAP immunohistochemistry (IHC) may be a surrogate marker of CDKN2A/B status. However, the association between CDKN2A/B and MTAP deletion at the genomic level remains unknown. We assessed CDKN2A/B and MTAP deletions by chromosomal microarray in 333 adult-type diffuse gliomas and performed MTAP IHC on a subset (n = 63). CDKN2A/B and MTAP deletions were detected in 216 and 215 cases, respectively, and were concurrent in 99.5% (215/216). While most tumors with CDKN2A/B homozygous deletion (n = 148) showed concurrent MTAP homozygous deletion (108/148; 73.0%), a subset harbored MTAP heterozygous deletion (39/148; 26.4%). By analyzing the size of the chromosomal alterations, we demonstrate that initial large chromosomal 9p losses result in concurrent heterozygous deletion of CDKN2A/B and MTAP whereas smaller \"second hit\" deletions leading to homozygous CDKN2A/B deletion do not always encompass the MTAP locus. Discordant CDKN2A/B and MTAP tumors affect the association between MTAP IHC and copy number status of MTAP and CDKN2A/B. These findings suggest that adult-type diffuse gliomas, regardless of IDH status, follow a stereotypic pathway involving concurrent CDKN2A/B and MTAP heterozygous deletion but may diverge for CDKN2A/B and MTAP homozygous deletion.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"551-560"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390351","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}

引用次数: 0

Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease. 机器学习量化阿尔茨海默病患者3个脑区的Aβ沉积的临床和病理相关性

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-06-01 DOI: 10.1093/jnen/nlaf152

David Garcia, Shivam Rajendra Rai Sharma, Naomi Saito, Laurel Beckett, Louise Nicole C Sevilla, La Rissa Vasquez, Charles S DeCarli, David Gutman, Juan Vizcarra, David G Coughlin, Andrew F Teich, Lorena Garcia, Dan M Mungas, Chen-Nee Chuah, Brittany N Dugger

{"title":"Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease.","authors":"David Garcia, Shivam Rajendra Rai Sharma, Naomi Saito, Laurel Beckett, Louise Nicole C Sevilla, La Rissa Vasquez, Charles S DeCarli, David Gutman, Juan Vizcarra, David G Coughlin, Andrew F Teich, Lorena Garcia, Dan M Mungas, Chen-Nee Chuah, Brittany N Dugger","doi":"10.1093/jnen/nlaf152","DOIUrl":"10.1093/jnen/nlaf152","url":null,"abstract":"Machine learning enables scalable quantification of neuropathology, offering deeper phenotyping of Alzheimer's disease (AD). In this validation study, we quantified amyloid-beta (Aβ) deposits, evaluating multiple brain regions across institutions, and evaluated associations with clinical, demographic, and genetic factors in persons pathologically diagnosed with AD. All linear models were adjusted for sex, age of death, ethnicity, and center. We analyzed densities (#/mm2) of cored plaques, diffuse plaques, and cerebral amyloid angiopathy (CAA) in 273 individuals from 3 Alzheimer's Disease Research Centers. Formalin-fixed paraffin-embedded sections of frontal, temporal, and parietal cortices were immunostained and digitized, generating 799 whole-slide images (WSIs). Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P < .001); the temporal cortex had the highest diffuse plaque (P < .001); CAA showed no regional differences. Wilcoxon rank-sum test, and covariates adjusted linear models showed ApoE ε4- status was associated with higher cored plaque densities in the temporal lobe (P = .04). ApoE ε4+ status was associated with diffuse plaques in the temporal lobe (P = .001), and CAA in the frontal lobe (P = .004). These findings provide further validation and provide exploratory associations advancing deeper phenotyping of AD.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"537-550"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433808","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}

引用次数: 0

A novel hierarchical framework elucidating regional differences in α-synuclein and tau co-pathology in military veterans with parkinsonism. 一个新的层次框架阐明了α-突触核蛋白和tau共同病理在退伍军人帕金森病中的区域差异。

IF 3.3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-06-01 DOI: 10.1093/jnen/nlaf137

Victoria G Flores Almazan, Klaudia F Laborc, Claudia De Sanctis, Emma L Thorn, Adam Goldstein, Alessandra Cervera, Dalilah F Quintana Mora, Yolfrankcis Mendez, Anya C McGoldrick, Lily Yu-Chia Chiu, Quazi I Hossain, Stephanie McQuillan, Kourtni Lind-Watson, Jamie M Walker, Ruth H Walker, Melissa J Nirenberg, John F Crary

{"title":"A novel hierarchical framework elucidating regional differences in α-synuclein and tau co-pathology in military veterans with parkinsonism.","authors":"Victoria G Flores Almazan, Klaudia F Laborc, Claudia De Sanctis, Emma L Thorn, Adam Goldstein, Alessandra Cervera, Dalilah F Quintana Mora, Yolfrankcis Mendez, Anya C McGoldrick, Lily Yu-Chia Chiu, Quazi I Hossain, Stephanie McQuillan, Kourtni Lind-Watson, Jamie M Walker, Ruth H Walker, Melissa J Nirenberg, John F Crary","doi":"10.1093/jnen/nlaf137","DOIUrl":"10.1093/jnen/nlaf137","url":null,"abstract":"Neuropathologic features diagnostic of parkinsonian disorders infrequently occur in isolation; hyperphosphorylated tau (p-tau) and amyloid plaques are often observed in combination with α-synuclein deposition. Co-pathologies in neurodegenerative diseases are now recognized as the norm rather than an exception, but existing neuropathological assessment tools do not capture the complexity of concurrent co-pathologies. Characterization of this co-pathology is critical, as it has the potential to identify synergistic mechanisms. We developed a hierarchical cytoarchitectural classification system, which we applied to an autopsy series of military veterans with parkinsonism (n = 26), focusing on Lewy and neurofibrillary pathologies. We defined co-pathology as Type A (co-morbid), Type B (co-regional), Type C (co-cellular), or Type D (co-aggregate). The regional distributions of each co-pathology subtype were assessed using double-label immunohistochemistry in the frontal cortex, hippocampal formation, and midbrain. The frontal cortex demonstrated only subtypes A-C (no co-aggregates), whereas the midbrain and hippocampus showed all subtypes of copathology (A-D). In summary, we show marked differences in the prevalence and levels of mixed α-synuclein and tau pathology in this cohort. Our classification system has the potential to be applied broadly for the study of co-pathology in neurodegenerative disorders.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"525-536"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878512","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}

引用次数: 0

Secondary atypical teratoid/rhabdoid tumors are not necessarily categorized as AT/RT by DNA methylation analysis. 继发性非典型畸胎瘤/横纹肌样瘤不一定通过DNA甲基化分析归类为AT/RT。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2026-05-29 DOI: 10.1093/jnen/nlag060

Haruna Okuno, Kohei Fukuoka, Keishiro Amano, Tsutomu Sugai, Ayako Yamazaki, Junko Hirato, Sumihito Nobusawa

引用次数: 0