Journal of Neuropathology and Experimental Neurology最新文献_第10页

Ferritin is closely associated with microglia in amyotrophic lateral sclerosis. 铁蛋白与肌萎缩侧索硬化症的小胶质细胞密切相关。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-11-01 DOI: 10.1093/jnen/nlae074

Ju Gao, Ogoegbunam Okolo, Sandra L Siedlak, Robert P Friedland, Xinglong Wang

{"title":"Ferritin is closely associated with microglia in amyotrophic lateral sclerosis.","authors":"Ju Gao, Ogoegbunam Okolo, Sandra L Siedlak, Robert P Friedland, Xinglong Wang","doi":"10.1093/jnen/nlae074","DOIUrl":"10.1093/jnen/nlae074","url":null,"abstract":"Iron deposition is a hallmark of amyotrophic lateral sclerosis (ALS) and has been strongly implicated in its pathogenesis. As a byproduct of cellular oxidative stress, iron dysregulation modifies basal levels of the regulatory iron-binding protein ferritin. Examination of thoracic and lumbar spinal cord tissues found increased ferritin immunostaining in white matter axons that corresponded to areas of increased microgliosis in 8 ALS patients versus 8 normal subjects. Gray matter areas containing the motor neurons also demonstrated increased ferritin and microglia in ALS compared to controls but at lower levels than in the white matter. Motor neurons with or without TDP-43 inclusions did not demonstrate either increased ferritin or associated microglial activation. We also observed an association of ferritin with microglia in cerebral cortical tissue samples of ALS cases and in the spinal cord tissues of transgenic mice expressing the SOD1G93A mutation. Elevated ferritin levels were detected in the insoluble fraction from spinal cord tissues of individuals with ALS. These findings suggest that activated microglia and increased ferritin may play significant roles in ALS progression since they are found closely associated in areas of axonal and cortical degeneration.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"917-926"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603742","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

Very low levels of ABCA7 in the cerebrum and Alzheimer's disease onset between the ages of 60 and 80 independently of APOE. 大脑中极低水平的 ABCA7 与阿尔茨海默病的发病年龄（60 至 80 岁）无关，与 APOE 无关。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae060

Viktor Garliyev, Catherine A Lyssenko, Joel P Wiener, Domenico Praticò, Nicholas N Lyssenko

{"title":"Very low levels of ABCA7 in the cerebrum and Alzheimer's disease onset between the ages of 60 and 80 independently of APOE.","authors":"Viktor Garliyev, Catherine A Lyssenko, Joel P Wiener, Domenico Praticò, Nicholas N Lyssenko","doi":"10.1093/jnen/nlae060","DOIUrl":"10.1093/jnen/nlae060","url":null,"abstract":"This cross-sectional study addressed the ABCA7-Alzheimer's disease (AD) association. ABCA7 protein levels were quantified in 3 cerebral regions of brain donors with Braak neurofibrillary tangle (NFT) stages 0-V. Ordinal regression models were implemented to estimate the effect of ABCA7 on stopping in an earlier Braak NFT stage versus progressing to the later stages in 2 prespecified age segments. In the final model, high ABCA7 levels in the parietal cortex increased the odds of remaining cognitively healthy (ie, in stages 0/I) versus experiencing AD onset (ie, progressing to stages II-V) in the 61-80 age segment (OR = 2.87, adj 95% CI = 1.41-7.86, adj P = .007, n = 109), after controlling for APOE and other covariates. No ABCA7-AD association was found in the 81-98 age segment (n = 113). Parietal ABCA7 levels in 61-80-year-old with stages II-V were very low, even significantly lower than in 81-98-year-old with stages II-V. ABCA7 levels in the prefrontal cortex and hippocampus predicted AD onset in the 61-80 age segment after adjustment for APOE. ABCA7 levels were also the lowest in 61-80-year-old with frequent neuritic plaques. Thus, very low ABCA7 levels in the cerebrum are associated with AD onset in the 7th-8th decade of life.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"808-821"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427043","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

FH-mutant glioma displaying the epigenetic signature of IDH-mutant astrocytomas. FH突变胶质瘤显示出IDH突变星形细胞瘤的表观遗传学特征。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae064

Valentina Zschernack, Christian Thomas, Christina Schaub, Glen Kristiansen, Andreas Waha, Tobias Goschzik, Ulrich Herrlinger, Torsten Pietsch

引用次数: 0

Cerebral amyloid-β-related angiitis and iatrogenic cerebral amyloid angiopathy-related vasculitis: Implications for amyloid-related imaging abnormalities. 脑淀粉样蛋白-β相关血管炎和先天性脑淀粉样血管病相关血管炎：淀粉样蛋白相关成像异常的意义。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae068

Rudy J Castellani, Pouya Jamshidi

引用次数: 0

Additive effects of mild head trauma, blast exposure, and aging within white matter tracts: A novel Diffusion Tensor Imaging analysis approach. 白质束内轻度头部创伤、爆炸暴露和衰老的叠加效应：新型扩散张量成像分析方法

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae069

Oren Poliva, Christian Herrera, Kelli Sugai, Nicole Whittle, Marjorie R Leek, Samuel Barnes, Barbara Holshouser, Alex Yi, Jonathan H Venezia

{"title":"Additive effects of mild head trauma, blast exposure, and aging within white matter tracts: A novel Diffusion Tensor Imaging analysis approach.","authors":"Oren Poliva, Christian Herrera, Kelli Sugai, Nicole Whittle, Marjorie R Leek, Samuel Barnes, Barbara Holshouser, Alex Yi, Jonathan H Venezia","doi":"10.1093/jnen/nlae069","DOIUrl":"10.1093/jnen/nlae069","url":null,"abstract":"Existing diffusion tensor imaging (DTI) studies of neurological injury following high-level blast exposure (hlBE) in military personnel have produced widely variable results. This is potentially due to prior studies often not considering the quantity and/or recency of hlBE, as well as co-morbidity with non-blast head trauma (nbHT). Herein, we compare commonly used DTI metrics: fractional anisotropy and mean, axial, and radial diffusivity, in Veterans with and without history of hlBE and/or nbHT. We use both the traditional method of dividing participants into 2 equally weighted groups and an alternative method wherein each participant is weighted by quantity and recency of hlBE and/or nbHT. While no differences were detected using the traditional method, the alternative method revealed diffuse and extensive changes in all DTI metrics. These effects were quantified within 43 anatomically defined white matter tracts, which identified the forceps minor, middle corpus callosum, acoustic and optic radiations, fornix, uncinate, inferior fronto-occipital and inferior longitudinal fasciculi, and cingulum, as the pathways most affected by hlBE and nbHT. Moreover, additive effects of aging were present in many of the same tracts suggesting that these neuroanatomical effects may compound with age.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"853-869"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759308","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

Cytoplasmic aggregation of TDP43 and topographic correlation with tau and α-synuclein accumulation in the rTg4510 mouse model of tauopathy. TDP43 的细胞质聚集以及与 rTg4510 小鼠 tauopathy 模型中 tau 和 α-synuclein 积累的地形相关性。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae063

Yutaro Nakayama, James K Chambers, Yuta Takaichi, Kazuyuki Uchida

{"title":"Cytoplasmic aggregation of TDP43 and topographic correlation with tau and α-synuclein accumulation in the rTg4510 mouse model of tauopathy.","authors":"Yutaro Nakayama, James K Chambers, Yuta Takaichi, Kazuyuki Uchida","doi":"10.1093/jnen/nlae063","DOIUrl":"10.1093/jnen/nlae063","url":null,"abstract":"In patients with TDP43 proteinopathy, phosphorylated TDP43 (p-TDP43) accumulates in the cytoplasm of neurons. The accumulation of p-TDP43 has also been reported in patients with tauopathy and α-synucleinopathy. We investigated spatiotemporal changes in p-TDP43 accumulation in the brains of rTg4510 mice that overexpressed human mutant tau (P301L) and exhibited hyperphosphorylated tau (hp-tau) and phosphorylated αSyn (p-αSyn) accumulation. Immunohistochemically, p-TDP43 aggregates were observed in the cytoplasm of neurons, which increased with age. A significant positive correlation was observed between the number of cells with p-TDP43 aggregates and hp-tau and p-αSyn aggregates. Suppression of the human mutant tau (P301L) expression by doxycycline treatment reduces the accumulation of p-TDP43, hp-tau, and p-αSyn. Proteinase K-resistant p-TDP43 aggregates were found in regions with high hp-tau, and p-αSyn accumulation. Western blotting of the sarkosyl-insoluble fraction revealed bands of monomeric TDP43 and p-TDP43. These results indicate that the accumulation of mouse p-TDP43 is associated with the accumulation of human mutant tau (P301L) in rTg4510 mouse brains. The accumulation of hp-tau and p-αSyn may promote sarkosyl-insoluble p-TDP43 aggregates that are resistant to proteinase K. The synergistic effects of tau, TDP43, and αSyn may be involved in the pathology of proteinopathies, leading to the accumulation of multiple abnormal proteins.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"833-842"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327610","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

Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration. 研究 TWSG1 在胶质瘤细胞恶性进展和肿瘤相关巨噬细胞浸润中的作用机制。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae067

Kuan Feng, Gengfan Ye, Hongcai Wang, Shiwei Li, Xuebin Wen, Maosong Chen

{"title":"Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration.","authors":"Kuan Feng, Gengfan Ye, Hongcai Wang, Shiwei Li, Xuebin Wen, Maosong Chen","doi":"10.1093/jnen/nlae067","DOIUrl":"10.1093/jnen/nlae067","url":null,"abstract":"Gliomas are malignant tumors of the central nervous system; current treatment methods have low efficacy. Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been shown to play a role in gliomas but it is not known whether TWSG1 participates in glioma pathogenesis and macrophage immune regulation. This study identified a total of 24 differentially expressed genes with survival differences in gliomas using bioinformatics analysis. Among them, TWSG1 exhibited the strongest correlation with gliomas and was positively correlated with macrophage enrichment. The results showed that TWSG1 was highly expressed in various glioma cell lines, with the highest expression observed in the A172 cell line. Silencing TWSG1 significantly decreased the viability, migration, and invasion of A172 cells in vitro and tumor growth in a mouse xenograft model in vivo. It also reduced the expression of the matrix metalloproteinases MMP2 and MMP9 both in vivo and in vitro. Silencing TWSG1 significantly reduced the expression of M2 macrophage makers and upregulated the expression of M1 macrophage markers in A172 cells and tumor tissues. These data suggest that interference with TWSG1 suppressed the progression of A172 glioma cells and regulated immune infiltration.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"843-852"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476835","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

Revealing the potential role of hsa-miR-663a in modulating the PI3K-Akt signaling pathway via miRNA microarray in spinal muscular atrophy patient fibroblast-derived iPSCs. 通过 miRNA 微阵列揭示 hsa-miR-663a 在脊髓性肌萎缩症患者成纤维细胞衍生 iPSCs 中调节 PI3K-Akt 信号通路的潜在作用。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae065

Gayatri Gandhi, Radha Kodiappan, Syahril Abdullah, Hoon Koon Teoh, Lihui Tai, Soon Keng Cheong, Wendy Wai Yeng Yeo

{"title":"Revealing the potential role of hsa-miR-663a in modulating the PI3K-Akt signaling pathway via miRNA microarray in spinal muscular atrophy patient fibroblast-derived iPSCs.","authors":"Gayatri Gandhi, Radha Kodiappan, Syahril Abdullah, Hoon Koon Teoh, Lihui Tai, Soon Keng Cheong, Wendy Wai Yeng Yeo","doi":"10.1093/jnen/nlae065","DOIUrl":"10.1093/jnen/nlae065","url":null,"abstract":"Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder due to deletion or mutation of survival motor neuron 1 (SMN1) gene. Although survival motor neuron 2 (SMN2) gene is still present in SMA patients, the production of full-length survival motor neuron (SMN) protein is insufficient owing to missing or mutated SMN1. No current disease-modifying therapies can cure SMA. The aim of this study was to explore microRNA (miRNA)-based therapies that may serve as a potential target for therapeutic intervention in delaying SMA progression or as treatment. The study screened for potentially dysregulated miRNAs in SMA fibroblast-derived iPSCs using miRNA microarray. Results from the miRNA microarray were validated using quantitative reverse transcription polymerase chain reaction. Bioinformatics analysis using various databases was performed to predict the potential putative gene targeted by hsa-miR-663a. The findings showed differential expression of hsa-miR-663a in SMA patients in relation to a healthy control. Bioinformatics analysis identified GNG7, IGF2, and TNN genes that were targeted by hsa-miR-663a to be involved in the PI3K-AKT pathway, which may be associated with disease progression in SMA. Thus, this study suggests the potential role of hsa-miR-663a as therapeutic target for the treatment of SMA patients in the near future.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"822-832"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419533","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

Primary CNS histiocytic sarcoma: Two case reports highlighting a novel MIGA2::BRAF gene fusion and genome-wide DNA methylation profiling results. 原发性中枢神经系统组织细胞肉瘤：两份病例报告突显新型 MIGA2::BRAF 基因融合和全基因组 DNA 甲基化分析结果。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae061

Ryan Cecchi, Doré Guptil, Nicholas Haslett, Alexandra Hristov, Jacob R Bledsoe, Harrison Tsai, John DeWitt, Sean P Ferris

引用次数: 0

In situ seeding assay: A novel technique for direct tissue localization of bioactive tau. 原位播种试验：生物活性 tau 的直接组织定位新技术。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-10-01 DOI: 10.1093/jnen/nlae059

Romain Perbet, Anastasie Mate de Gerando, Calina Glynn, Cameron Donahue, Angelica Gaona, Raquel N Taddei, Teresa Gomez-Isla, Aurelien Lathuiliere, Bradley T Hyman

{"title":"In situ seeding assay: A novel technique for direct tissue localization of bioactive tau.","authors":"Romain Perbet, Anastasie Mate de Gerando, Calina Glynn, Cameron Donahue, Angelica Gaona, Raquel N Taddei, Teresa Gomez-Isla, Aurelien Lathuiliere, Bradley T Hyman","doi":"10.1093/jnen/nlae059","DOIUrl":"10.1093/jnen/nlae059","url":null,"abstract":"Proteins exhibiting prion-like properties are implicated in tauopathies. The prion-like traits of tau influence disease progression and correlate with severity. Techniques to measure tau bioactivity such as RT-QuIC and biosensor cells lack spatial specificity. Therefore, we developed a histological probe aimed at detecting and localizing bioactive tau in situ. We first induced the recruitment of a tagged probe by bioactive Tau in human brain tissue slices using biosensor cell lysates containing a fluorescent probe. We then enhanced sensitivity and flexibility by designing a recombinant probe with a myc tag. The probe design aimed to replicate the recruitment process seen in prion-like mechanisms based on the cryo-EM structure of tau aggregates in Alzheimer disease (AD). Using this novel probe, we observed selective staining of misfolded tau in pre- and post-synaptic structures within neurofibrillary tangles and neurites, whether or not associated with neuritic plaques. The probe specifically targeted AD-associated bioactive tau and did not recognize bioactive tau from other neurodegenerative diseases. Electron microscopy and immunolabeling further confirmed the identification of fibrillar and non-fibrillar tau. Finally, we established a correlation between quantifying bioactive tau using this technique and gold standard biosensor cells. This technique presents a robust approach for detecting bioactive tau in AD tissues and has potential applications for deciphering mechanisms of tau propagation and degradation pathways.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"870-881"},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450667","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