Paul Benjamin Loughrey, Christine Greene, Kris D McCombe, Fatima Abdullahi Sidi, Stephen McQuaid, Stephen Cooke, Steven J Hunter, Brian Herron, Márta Korbonits, Stephanie G Craig, Jacqueline A James
Pituitary neuroendocrine tumour Ki-67 proliferation index varies according to the number of tumour cells assessed. Consistent Ki-67 scoring approaches and re-evaluation of the recommended Ki-67 3% cut-off are required to clarify controversies in pituitary neuroendocrine tumour Ki-67 proliferation index assessment.
July 15, 2024: Brain Pathology
Aya Murakami, Shunsuke Koga, Shinsuke Fujioka, Adrianna E White, Kevin F Bieniek, Hiroaki Sekiya, Mariely DeJesus-Hernandez, NiCole A Finch, Marka van Blitterswijk, Masataka Nakamura, Yoshio Tsuboi, Melissa E Murray, Zbigniew K Wszolek, Dennis W Dickson
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN-dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN-predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN-predominant MND...
July 10, 2024: Brain Pathology
Olivia M Rifai, Fergal M Waldron, Danah Sleibi, Judi O'Shaughnessy, Danielle J Leighton, Jenna M Gregory
Many genes have been linked to amyotrophic lateral sclerosis (ALS), including never in mitosis A (NIMA)-related kinase 1 (NEK1), a serine/threonine kinase that plays a key role in several cellular functions, such as DNA damage response and cell cycle regulation. Whole-exome sequencing studies have shown that NEK1 mutations are associated with an increased risk for ALS, where a significant enrichment of NEK1 loss-of-function (LOF) variants were found in individuals with ALS compared to controls. In particular, the p...
July 10, 2024: Brain Pathology
Nadja Straumann, Benjamin F Combes, Xose Luis Dean Ben, Rebecca Sternke-Hoffmann, Juan A Gerez, Ines Dias, Zhenyue Chen, Benjamin Watts, Iman Rostami, Kuangyu Shi, Axel Rominger, Christian R Baumann, Jinghui Luo, Daniela Noain, Roger M Nitsch, Nobuyuki Okamura, Daniel Razansky, Ruiqing Ni
Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo...
July 9, 2024: Brain Pathology
Jan-Kolja Strecker, Antje Schmidt-Pogoda, Kai Diederich, Dario Zaremba, Frederique Wieters, Carolin Beuker, Mailin Hannah Marie Koecke, Frederike Anne Straeten, Heinz Wiendl, Jens Minnerup
Demyelination of corticospinal tract neurons contributes to long-term disability after cortical stroke. Nonetheless, poststroke myelin loss has not been addressed as a therapeutic target, so far. We hypothesized that an antibody-mediated inhibition of the Nogo receptor-interacting protein (LINGO-1, leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein) may counteract myelin loss, enhance remyelination and axonal growth, and thus promote functional recovery following stroke...
June 30, 2024: Brain Pathology
Manuela Ceccarelli, Sabrina Rossi, Fabrizio Bonaventura, Roberto Massari, Annunziata D'Elia, Andrea Soluri, Laura Micheli, Giorgio D'Andrea, Barbara Mancini, Marcello Raspa, Ferdinando Scavizzi, Rita Alaggio, Francesca Del Bufalo, Evelina Miele, Andrea Carai, Angela Mastronuzzi, Felice Tirone
The prognosis for many pediatric brain tumors, including cerebellar medulloblastoma (MB), remains dismal but there is promise in new therapies. We have previously generated a mouse model developing spontaneous MB at high frequency, Ptch1+/- /Tis21-/- . In this model, reproducing human tumorigenesis, we identified the decline of the Cxcl3 chemokine in cerebellar granule cell precursors (GCPs) as responsible for a migration defect, which causes GCPs to stay longer in the proliferative area rather than differentiate and migrate internally, making them targets of transforming insults...
June 30, 2024: Brain Pathology
Diana G Bohannon, Danielle Long, Hamid R Okhravi, Sunhee C Lee, Christopher Lawrence De Jesus, Thomas A Neubert, Agueda A Rostagno, Jorge A Ghiso, Woong-Ki Kim
Although the concept that the blood-brain barrier (BBB) plays an important role in the etiology and pathogenesis of Alzheimer's disease (AD) has become increasingly accepted, little is known yet about how it actually contributes. We and others have recently identified a novel functionally distinct subset of BBB pericytes (PCs). In the present study, we sought to determine whether these PC subsets differentially contribute to AD-associated pathologies by immunohistochemistry and amyloid beta (Aβ) peptidomics...
June 27, 2024: Brain Pathology
Alejandro Martín-Belmonte, Carolina Aguado, Rocío Alfaro-Ruiz, Akos Kulik, Luis de la Ossa, Ana Esther Moreno-Martínez, Samuel Alberquilla, Lucía García-Carracedo, Miriam Fernández, Ana Fajardo-Serrano, Ester Aso, Ryuichi Shigemoto, Eduardo D Martín, Yugo Fukazawa, Francisco Ciruela, Rafael Luján
Voltage-gated CaV 2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of CaV 2.1 channels in the hippocampus in association with GABAB receptors...
June 17, 2024: Brain Pathology
Longhong Zhu, Dazhang Bai, Xiang Wang, Kaili Ou, Bang Li, Qingqing Jia, Zhiqiang Tan, Jiahui Liang, Dajian He, Sen Yan, Lu Wang, Shihua Li, Xiao-Jiang Li, Peng Yin
Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells...
May 23, 2024: Brain Pathology
Davide Mulone, Rita Polati, Evelina Miele, Sara Patrizi, Andrea Mafficini, Valeria Barresi
No abstract text is available yet for this article.
May 20, 2024: Brain Pathology
Lieke Jäkel, Kiki K W J Claassen, Anna M De Kort, Wilmar M T Jolink, Yannick Vermeiren, Floris H B M Schreuder, Benno Küsters, Catharina J M Klijn, H Bea Kuiperij, Marcel M Verbeek
Decreased microvascular levels of claudin-5 in the occipital and temporal lobe of patients with cerebral amyloid angiopathy are associated with intracerebral haemorrhage.
May 19, 2024: Brain Pathology
Kiyoshi Ito, Mitsunori Yamada, Kai Uehara, Yusuke Takahashi, Minori Kodaira, Yoshiki Sekijima, Yasuko Toyoshima, Akiyoshi Kakita, Kunihiko Makino, Hiroki Ohashi, Kazuhiro Hongo, Tetsuyoshi Horiuchi
The figure shows tissue samples taken from three previous cases, revealing the cause of hemosiderin deposition in the central nervous system because of superficial siderosis.
May 9, 2024: Brain Pathology
Caitlyn Fastenau, Madison Bunce, Mallory Keating, Jessica Wickline, Sarah C Hopp, Kevin F Bieniek
Glycosylation is the most common form of post-translational modification in the brain. Aberrant glycosylation has been observed in cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) cases, including dysregulation of terminal sialic acid (SA) modifications. While alterations in sialylation have been identified in AD, the localization of SA modifications on cellular or aggregate-associated glycans is largely unknown because of limited spatial resolution of commonly utilized methods. The present study aims to overcome these limitations with novel combinations of histologic techniques to characterize the sialylation landscape of O- and N-linked glycans in autopsy-confirmed AD post-mortem brain tissue...
May 9, 2024: Brain Pathology
Petr Vymola, Elena Garcia-Borja, Jakub Cervenka, Eva Balaziova, Barbora Vymolova, Jana Veprkova, Petr Vodicka, Helena Skalnikova, Robert Tomas, David Netuka, Petr Busek, Aleksi Sedo
Gliomagenesis induces profound changes in the composition of the extracellular matrix (ECM) of the brain. In this study, we identified a cellular population responsible for the increased deposition of collagen I and fibronectin in glioblastoma. Elevated levels of the fibrillar proteins collagen I and fibronectin were associated with the expression of fibroblast activation protein (FAP), which is predominantly found in pericyte-like cells in glioblastoma. FAP+ pericyte-like cells were present in regions rich in collagen I and fibronectin in biopsy material and produced substantially more collagen I and fibronectin in vitro compared to other cell types found in the GBM microenvironment...
May 5, 2024: Brain Pathology
Lorraina J Robinson, Eric Goold, David Anderson, Robert C Rennert, William T Couldwell, Changhong Xing
No abstract text is available yet for this article.
May 2024: Brain Pathology
Takashi Ando, Yuichi Riku, Akio Akagi, Hiroaki Miyahara, Takashi Uematsu, Ikuko Aiba, Jun Sone, Masahisa Katsuno, Mari Yoshida, Yasushi Iwasaki
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA. We examined 97 spinal cords from consecutively autopsied patients with MSA...
May 2024: Brain Pathology
Marco Pisa, Joseph L Watson, Jonathan I Spencer, Guy Niblett, Yasamin Mahjoub, Andrew Lockhart, Richard L Yates, Sydney A Yee, Gina Hadley, Jennifer Ruiz, Margaret M Esiri, Benedict Kessler, Roman Fischer, Gabriele C DeLuca
Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA-DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA-DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA-DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA-DRB*15-positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation...
April 25, 2024: Brain Pathology
Thomas Comptdaer, Meryem Tardivel, Claire Schirmer, Luc Buée, Marie-Christine Galas
While the double helical structure has long been its iconic representation, DNA is structurally dynamic and can adopt alternative secondary configurations. Specifically, guanine-rich DNA sequences can fold in guanine quadruplexes (G4) structures. These G4 play pivotal roles as regulators of gene expression and genomic stability, and influence protein homeostasis. Despite their significance, the association of G4 with neurodegenerative diseases such as Alzheimer's disease (AD) has been underappreciated. Recent findings have identified DNA sequences predicted to form G4 in sarkosyl-insoluble aggregates from AD brains, questioning the involvement of G4-structured DNA (G4 DNA) in the pathology...
April 22, 2024: Brain Pathology
(no author information available yet)
No abstract text is available yet for this article.
April 22, 2024: Brain Pathology
Qi-Jie Zhang, Jie Lin, You-Liang Wang, Long Chen, Ying Ding, Fu-Ze Zheng, Huan-Huan Song, Ao-Wei Lv, Yu-Ying Li, Qi-Fu Guo, Min-Ting Lin, Wei Hu, Liu-Qing Xu, Wen-Long Zhao, Ling Fang, Meng-Chao Cui, Zhi-Fei Fu, Wan-Jin Chen, Jing Zhang, Zhi-Qiang Wang, Ning Wang, Ying Fu
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients...
April 11, 2024: Brain Pathology
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