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Journal Acta Neuropathol Commun

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The association of Lewy bodies with limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes and their role in cognition and Alzheimer's dementia in older persons.

Sonal Agrawal, Lei Yu, Sukriti Nag, Konstantinos Arfanakis, Lisa L Barnes, David A Bennett, Julie A Schneider,

Lewy bodies (LBs) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are common in older persons and associated with cognitive impairment. However, little is known about the relationship between LBs and LATE-NC and their combined roles in cognitive impairment and Alzheimer's dementia in community-dwelling participants. The study included 1670 community-based ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):156]

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The intracellular milieu of Parkinson's disease patient brain cells modulates alpha-synuclein protein aggregation.

Nadja Gustavsson, Ekaterina Savchenko, Oxana Klementieva, Laurent Roybon,

Recent studies suggest that brain cell type specific intracellular environments may play important roles in the generation of structurally different protein aggregates that define neurodegenerative diseases. Using human induced pluripotent stem cells (hiPSC) and biochemical and vibrational spectroscopy techniques, we studied whether Parkinson's disease (PD) patient genomes could modulate alpha-synuclein ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):153]

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Analysis of genes (TMEM106B, GRN, ABCC9, KCNMB2, and APOE) implicated in risk for LATE-NC and hippocampal sclerosis provides pathogenetic insights: a retrospective genetic association study.

Adam J Dugan, Peter T Nelson, Yuriko Katsumata, Lincoln M P Shade, Kevin L Boehme, Merilee A Teylan, Matthew D Cykowski, Shubhabrata Mukherjee, John S K Kauwe, Timothy J Hohman, Julie A Schneider, , David W Fardo,

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):152]

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Exogenous Aβ seeds induce Aβ depositions in the blood vessels rather than the brain parenchyma, independently of Aβ strain-specific information.

Tsuyoshi Hamaguchi, Jee Hee Kim, Akane Hasegawa, Ritsuko Goto, Kenji Sakai, Kenjiro Ono, Yoshinori Itoh, Masahito Yamada,

Little is known about the effects of parenchymal or vascular amyloid β peptide (Aβ) deposition in the brain. We hypothesized that Aβ strain-specific information defines whether Aβ deposits on the brain parenchyma or blood vessels. We investigated 12 autopsied patients with different severities of Aβ plaques and cerebral amyloid angiopathy ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):151]

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Immune cell deconvolution of bulk DNA methylation data reveals an association with methylation class, key somatic alterations, and cell state in glial/glioneuronal tumors.

Omkar Singh, Drew Pratt, Kenneth Aldape,

It is recognized that the tumor microenvironment (TME) plays a critical role in the biology of cancer. To better understand the role of immune cell components in CNS tumors, we applied a deconvolution approach to bulk DNA methylation array data in a large set of newly profiled samples (n = 741) as ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):148]

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A recurrent RYR1 mutation associated with early-onset hypotonia and benign disease course.

Valérie Biancalana, John Rendu, Annabelle Chaussenot, Helen Mecili, Eric Bieth, Mélanie Fradin, Sandra Mercier, Maud Michaud, Marie-Christine Nougues, Laurent Pasquier, Sabrina Sacconi, Norma B Romero, Pascale Marcorelles, François Jérôme Authier, Antoinette Gelot Bernabe, Emmanuelle Uro-Coste, Claude Cances, Bertrand Isidor, Armelle Magot, Marie-Christine Minot-Myhie, Yann Péréon, Julie Perrier-Boeswillwald, Gilles Bretaudeau, Nicolas Dondaine, Alison Bouzenard, Mégane Pizzimenti, Bruno Eymard, Ana Ferreiro, Jocelyn Laporte, Julien Fauré, Johann Böhm,

The ryanodine receptor RyR1 is the main sarcoplasmic reticulum Ca<sup>2+</sup> channel in skeletal muscle and acts as a connecting link between electrical stimulation and Ca<sup>2+</sup>-dependent muscle contraction. Abnormal RyR1 activity compromises normal muscle function and results in various human disorders including malignant hyperthermia, central core disease, and centronuclear myopathy. However, ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):155]

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Prion strains associated with iatrogenic CJD in French and UK human growth hormone recipients.

Jean-Yves Douet, Alvina Huor, Hervé Cassard, Séverine Lugan, Naïma Aron, Chloé Mesic, Didier Vilette, Tomás Barrio, Nathalie Streichenberger, Armand Perret-Liaudet, Marie-Bernadette Delisle, Patrice Péran, Jean-Philippe Deslys, Emmanuel Comoy, Jean-Luc Vilotte, Katayoun Goudarzi, Vincent Béringue, Marcelo A Barria, Diane L Ritchie, James W Ironside, Olivier Andréoletti,

Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):145]

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Synaptic tau: A pathological or physiological phenomenon?

Miranda Robbins, Emma Clayton, Gabriele S Kaminski Schierle,

In this review, we discuss the synaptic aspects of Tau pathology occurring during Alzheimer's disease (AD) and how this may relate to memory impairment, a major hallmark of AD. Whilst the clinical diagnosis of AD patients is a loss of working memory and long-term declarative memory, the histological diagnosis is ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):149]

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Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis.

Neevika Manoharan, Pamela Ajuyah, Akanksha Senapati, Marie Wong, Anna Mullins, Michael Rodriguez, Helen Doyle, Geoff McCowage, Loretta M S Lau, Paul G Ekert, David S Ziegler,

Diffuse leptomeningeal glioneuronal tumours (DLGNT) represent rare enigmatic CNS tumours of childhood. Most patients with this disease share common radiological and histopathological features but the clinical course of this disease is variable. A radiological hallmark of this disease is widespread leptomeningeal enhancement that may involve the entire neuroaxis with predilection ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):147]

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Disease-, region- and cell type specific diversity of α-synuclein carboxy terminal truncations in synucleinopathies.

Ethan W Hass, Zachary A Sorrentino, Yuxing Xia, Grace M Lloyd, John Q Trojanowski, Stefan Prokop, Benoit I Giasson,

Synucleinopathies, including Parkinson's disease (PD), Lewy body dementia (LBD), Alzheimer's disease with amygdala restricted Lewy bodies (AD/ALB), and multiple system atrophy (MSA) comprise a spectrum of neurodegenerative disorders characterized by the presence of distinct pathological α-synuclein (αSyn) inclusions. Experimental and pathological studies support the notion that αSyn aggregates contribute to ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):146]

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Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS.

Sarah Waters, Molly E V Swanson, Birger V Dieriks, Yibin B Zhang, Natasha L Grimsey, Helen C Murray, Clinton Turner, Henry J Waldvogel, Richard L M Faull, Jiyan An, Robert Bowser, Maurice A Curtis, Mike Dragunow, Emma Scotter,

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. The pattern of lower motor neuron loss along the spinal cord follows the pattern of deposition of phosphorylated TDP-43 aggregates. The blood-spinal cord barrier (BSCB) restricts entry into the spinal cord parenchyma ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):144]

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Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas.

Xin Wei, Michaël H Meel, Marjolein Breur, Marianna Bugiani, Esther Hulleman, Timothy N Phoenix,

The blood-brain barrier (BBB) plays important roles in brain tumor pathogenesis and treatment response, yet our understanding of its function and heterogeneity within or across brain tumor types remains poorly characterized. Here we analyze the neurovascular unit (NVU) of pediatric high-grade glioma (pHGG) and diffuse midline glioma (DMG) using patient ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):142]

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Forebrain Shh overexpression improves cognitive function and locomotor hyperactivity in an aneuploid mouse model of Down syndrome and its euploid littermates.

Feng J Gao, Donna Klinedinst, Fabian-Xosé Fernandez, Bei Cheng, Alena Savonenko, Benjamin Devenney, Yicong Li, Dan Wu, Martin G Pomper, Roger H Reeves,

Down syndrome (DS) is the leading genetic cause of intellectual disability and causes early-onset dementia and cerebellar hypoplasia. The prevalence of attention deficit hyperactivity disorder is elevated in children with DS. The aneuploid DS mouse model "Ts65Dn" shows prominent brain phenotypes, including learning and memory deficits, cerebellar hypoplasia, and locomotor ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):137]

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Deep learning assisted quantitative assessment of histopathological markers of Alzheimer's disease and cerebral amyloid angiopathy.

Valentina Perosa, Ashley A Scherlek, Mariel G Kozberg, Lindsey Smith, Thomas Westerling-Bui, Corinne A Auger, Serge Vasylechko, Steven M Greenberg, Susanne J van Veluw,

Traditionally, analysis of neuropathological markers in neurodegenerative diseases has relied on visual assessments of stained sections. Resulting semiquantitative scores often vary between individual raters and research centers, limiting statistical approaches. To overcome these issues, we have developed six deep learning-based models, that identify some of the most characteristic markers of ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):141]

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Experimental colitis promotes sustained, sex-dependent, T-cell-associated neuroinflammation and parkinsonian neuropathology.

Madelyn C Houser, W Michael Caudle, Jianjun Chang, George T Kannarkat, Yuan Yang, Sean D Kelly, Danielle Oliver, Valerie Joers, Kathleen M Shannon, Ali Keshavarzian, Malú Gámez Tansey,

<h4>Background</h4>The etiology of sporadic Parkinson's disease (PD) remains uncertain, but genetic, epidemiological, and physiological overlap between PD and inflammatory bowel disease suggests that gut inflammation could promote dysfunction of dopamine-producing neurons in the brain. Mechanisms behind this pathological gut-brain effect and their interactions with sex and with environmental factors are ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):139]

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Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery.

Mandana Hunter, Krista J Spiller, Myrna A Dominique, Hong Xu, Francis W Hunter, Terry C Fang, Rebecca G Canter, Christopher J Roberts, Richard M Ransohoff, John Q Trojanowski, Virginia M-Y Lee,

The microglial reaction is a hallmark of neurodegenerative conditions, and elements thereof may exert differential effects on disease progression, either worsening or ameliorating severity. In amyotrophic lateral sclerosis (ALS), a syndrome characterized by cytoplasmic aggregation of TDP-43 protein and atrophy of motor neurons in the cortex and spinal cord, the ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):140]

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Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions.

Arnault Tauziède-Espariat, Aurore Siegfried, Yvan Nicaise, Thomas Kergrohen, Philipp Sievers, Alexandre Vasiljevic, Alexandre Roux, Edouard Dezamis, Chiara Benevello, Marie-Christine Machet, Sophie Michalak, Chloe Puiseux, Francisco Llamas-Gutierrez, Pierre Leblond, Franck Bourdeaut, Jacques Grill, Christelle Dufour, Léa Guerrini-Rousseau, Samuel Abbou, Volodia Dangouloff-Ros, Nathalie Boddaert, Raphaël Saffroy, Lauren Hasty, Ellen Wahler, Mélanie Pagès, Felipe Andreiuolo, Emmanuèle Lechapt, Fabrice Chrétien, Thomas Blauwblomme, Kévin Beccaria, Johan Pallud, Stéphanie Puget, Emmanuelle Uro-Coste, Pascale Varlet, ,

The cIMPACT-NOW Update 7 has replaced the WHO nosology of "ependymoma, RELA fusion positive" by "Supratentorial-ependymoma, C11orf95-fusion positive". This modification reinforces the idea that supratentorial-ependymomas exhibiting fusion that implicates the C11orf95 (now called ZFTA) gene with or without the RELA gene, represent the same histomolecular entity. A hot off the ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):135]

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The pathogenic role of c-Kit+ mast cells in the spinal motor neuron-vascular niche in ALS.

Mariángeles Kovacs, Catalina Alamón, Cecilia Maciel, Valentina Varela, Sofía Ibarburu, Lucas Tarragó, Peter H King, Ying Si, Yuri Kwon, Olivier Hermine, Luis Barbeito, Emiliano Trias,

Degeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):136]

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Single-cell multimodal analysis in a case with reduced penetrance of Progranulin-Frontotemporal Dementia.

Karthick Natarajan, Jesper Eisfeldt, Maria Hammond, José Miguel Laffita-Mesa, Kalicharan Patra, Behzad Khoshnood, Linn Öijerstedt, Caroline Graff,

We identified an autosomal dominant progranulin mutation carrier without symptoms of dementia in her lifetime (Reduced Penetrance Mutation Carrier, RedPenMC). This resistance to develop expected pathology presents a unique opportunity to interrogate neurodegenerative mechanisms. We performed multimodal single-nuclei analyses of post-mortem frontal cortex from RedPenMC, including transcriptomics and global levels ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):132]

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Protein farnesylation is upregulated in Alzheimer's human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer's model mice.

Angela Jeong, Shaowu Cheng, Rui Zhong, David A Bennett, Martin O Bergö, Ling Li,

The pathogenic mechanisms underlying the development of Alzheimer's disease (AD) remain elusive and to date there are no effective prevention or treatment for AD. Farnesyltransferase (FT) catalyzes a key posttranslational modification process called farnesylation, in which the isoprenoid farnesyl pyrophosphate is attached to target proteins, facilitating their membrane localization and ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):129]

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Loss with ageing but preservation of frontal cortical capillary pericytes in post-stroke dementia, vascular dementia and Alzheimer's disease.

Ren Ding, Yoshiki Hase, Matthew Burke, Vincent Foster, William Stevenson, Tuomo Polvikoski, Raj N Kalaria,

Cerebral pericytes are an integral component of the neurovascular unit, which governs the blood-brain barrier. There is paucity of knowledge on cortical pericytes across different dementias. We quantified cortical pericytes in capillaries in 124 post-mortem brains from subjects with post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer's disease (AD) and AD-VaD ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):130]

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Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice.

Cristina Cudalbu, Pierre Bady, Marta Lai, Lijing Xin, Olga Gusyatiner, Marie-France Hamou, Mario Lepore, Jean-Philippe Brouland, Roy T Daniel, Andreas F Hottinger, Monika E Hegi,

The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):133]

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Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review.

Hulya Ulugut, Anke A Dijkstra, Marta Scarioni, , Frederik Barkhof, Philip Scheltens, Annemieke J M Rozemuller, Yolande A L Pijnenburg,

Although the right temporal variant frontotemporal dementia (rtvFTD) is characterised by distinct clinical and radiological features, its underlying histopathology remains elusive. Being considered a right-sided variant of semantic variant primary progressive aphasia (svPPA), TDP-43 type C pathology has been linked to the syndrome, but this has not been studied in ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):131]

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Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study.

Amer Toutonji, Mamatha Mandava, Silvia Guglietta, Stephen Tomlinson,

Activation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):126]

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Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

L E M Wisse, S Ravikumar, R Ittyerah, S Lim, J Lane, M L Bedard, L Xie, S R Das, T Schuck, M Grossman, E B Lee, M D Tisdall, K Prabhakaran, J A Detre, G Mizsei, J Q Trojanowski, E Artacho-Pérula, M M de Iñiguez de Onzono Martin, M M Arroyo-Jiménez, M Muñoz Lopez, F J Molina Romero, M P Marcos Rabal, S Cebada Sánchez, J C Delgado González, C de la Rosa Prieto, M Córcoles Parada, D A Wolk, D J Irwin, R Insausti, P A Yushkevich,

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were ... Read more >>

Acta Neuropathol Commun (Acta neuropathologica communications)
[2021, 9(1):128]

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