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Modelling pathological spread through the structural connectome in the frontotemporal dementia clinical spectrum Brain (IF 10.6) Pub Date : 2024-11-29 Federica Agosta, Silvia Basaia, Edoardo G Spinelli, Federica Facente, Laura Lumaca, Alma Ghirelli, Elisa Canu, Veronica Castelnovo, Elisa Sibilla, Chiara Tripodi, Fabiola Freri, Giordano Cecchetti, Giuseppe Magnani, Francesca Caso, Federico Verde, Nicola Ticozzi, Vincenzo Silani, Paola Caroppo, Sara Prioni, Cristina Villa, Lucio Tremolizzo, Ildebrando Appollonio, Ashish Raj, Massimo Filippi
The ability to predict the pathology spreading in patients with frontotemporal dementia (FTD) is crucial for early diagnosis and targeted interventions. This study examined the relationship between network vulnerability and longitudinal atrophy progression in FTD patients, using Network Diffusion Model (NDM) of pathology spread. Thirty behavioural-variant FTD (bvFTD), 13 semantic-variant primary progressive
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Cortico-thalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor Brain (IF 10.6) Pub Date : 2024-11-27 Shenghong He, Timothy O West, Fernando R Plazas, Laura Wehmeyer, Alek Pogosyan, Alceste Deli, Christoph Wiest, Damian M Herz, Thomas Simpson, Pablo Andrade, Fahd Baig, Michael G Hart, Francesca Morgante, James J FitzGerald, Michael T Barbe, Veerle Visser-Vandewalle, Alexander L Green, Erlick A Pereira, Hayriye Cagnan, Huiling Tan
Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation
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Eighty-six billion and counting: do we know the number of neurons in the human brain? Brain (IF 10.6) Pub Date : 2024-11-26 Alain Goriely
Through statistical analysis and comparison of different studies, Alain Goriely challenges the widely accepted figure of 86 billion neurons in the human brain, and argues that the actual number is uncertain, with estimates ranging between 61 and 99 billion.
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Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine Brain (IF 10.6) Pub Date : 2024-11-25 Abhilasha Vishwanath, Mitchell J Bartlett, Torsten Falk, Stephen L Cowen
Gamma band and single-unit neural activity in primary motor cortex (M1) are involved in the control of movement. This activity is disrupted in Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID), a debilitating consequence of dopamine replacement therapy for PD. Physiological features of LID include pathological narrowband gamma oscillations, finely tuned gamma (FTG), and altered M1 firing
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Correction to: Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma. Brain (IF 10.6) Pub Date : 2024-11-22
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Hypometabolic mismatch with atrophy and tau pathology in mixed Alzheimer and Lewy body disease Brain (IF 10.6) Pub Date : 2024-11-22 Michael Tran Duong, Sandhitsu R Das, Pulkit Khandelwal, Xueying Lyu, Long Xie, Emily McGrew, Nadia Dehghani, Corey T McMillan, Edward B Lee, Leslie M Shaw, Paul A Yushkevich, David A Wolk, Ilya M Nasrallah
Polypathology is a major driver of heterogeneity in clinical presentation and extent of neurodegeneration (N) in patients with Alzheimer Disease (AD). Beyond amyloid (A) and tau (T) pathologies, over half of patients with AD have concomitant pathology such as α-synuclein (S) in mixed AD with Lewy Body Disease (LBD). Patients with Mixed Etiology Dementia (MED) such as AD+LBD have faster progression
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Lewy pathology formation in patient-derived GBA1 Parkinson’s disease midbrain organoids Brain (IF 10.6) Pub Date : 2024-11-21 Emanuele Frattini, Gaia Faustini, Gianluca Lopez, Emma V Carsana, Mattia Tosi, Ilaria Trezzi, Manuela Magni, Giulia Soldà, Letizia Straniero, Daniele Facchi, Maura Samarani, Mitchell Martá-Ariza, Chiara M G De Luca, Elena Vezzoli, Alessandra Pittaro, Astghik Stepanyan, Rosamaria Silipigni, Isabel Rosety, Jens C Schwamborn, Sergio P Sardi, Fabio Moda, Stefania Corti, Giacomo P Comi, Fabio Blandini,
Fibrillary aggregation of α-synuclein in Lewy body inclusions and nigrostriatal dopaminergic neuron degeneration define Parkinson’s disease neuropathology. Mutations in GBA1, encoding glucocerebrosidase, are the most frequent genetic risk factor for Parkinson’s disease. However, the lack of reliable experimental models able to reproduce key neuropathological signatures has hampered the clarification
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Proteostasis restoration: a new metric for tau immunotherapy efficacy Brain (IF 10.6) Pub Date : 2024-11-21 Geoffrey Canet, Emmanuel Planel
This scientific commentary refers to ‘Proteostasis as a fundamental principle of Tau immunotherapy’ by Cruz et al. (https://doi.org/10.1093/brain/awae254).
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Why inflammatory reductionism is a threat to psychiatry (and the rest of medicine) Brain (IF 10.6) Pub Date : 2024-11-21 Thomas A Pollak
Thomas Pollak explores the emergence of a new worldview which attempts to explain all manner of ills as the result of inflammation or immune dysfunction. He argues that while this view is rooted in science, it neglects the true complexity of most health conditions, and risks undermining the more holistic concepts of illness favoured by psychiatry.
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Correction to: GDF5 as a rejuvenating treatment for age-related neuromuscular failure. Brain (IF 10.6) Pub Date : 2024-11-20
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The emerging field of non-invasive brain stimulation in Alzheimer’s disease Brain (IF 10.6) Pub Date : 2024-11-20 Giacomo Koch, Daniele Altomare, Alberto Benussi, Lucie Bréchet, Elias P Casula, Alessandra Dodich, Michela Pievani, Emiliano Santarnecchi, Giovanni B Frisoni
Treating cognitive impairment is a holy grail of modern clinical neuroscience. In the past few years, non-invasive brain stimulation is increasingly emerging as a therapeutic approach to ameliorate performance in patients with cognitive impairment and as an augmentation approach in persons whose cognitive performance is within normal limits. In patients with Alzheimer’s disease, better understanding
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Synaptic and cognitive impairment associated with L444P heterozygous glucocerebrosidase mutation Brain (IF 10.6) Pub Date : 2024-11-20 Wudu Lado, Ahrom Ham, Hongyu Li, Hong Zhang, Audrey Yuen Chang, Sergio Pablo Sardi, Roy N Alcalay, Ottavio Arancio, Serge Przedborsky, Guomei Tang
Cognitive impairment is a common but poorly understood non-motor aspect of Parkinson’s disease, negatively affecting patient’s functional capacity and quality of life. The mechanisms underlying cognitive impairment in Parkinson’s disease are still elusive, limiting treatment and prevention strategies. This study investigates the molecular and cellular basis of cognitive impairment associated with heterozygous
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Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy Brain (IF 10.6) Pub Date : 2024-11-18 Marnix Franken, Erik van der Wal, Dongxu Zheng, Bianca den Hamer, Patrick J van der Vliet, Richard J L F Lemmers, Anita van den Heuvel, Alexandra L Dorn, Cas G A Duivenvoorden, Stijn L M in’t Groen, Christian Freund, Bert Eussen, Rabi Tawil, Baziel G M van Engelen, Pim W W M P Pijnappel, Silvère M van der Maarel, Jessica C de Greef
Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads
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Single-nucleus transcriptomics reveals disease- and pathology-specific signatures in α-synucleinopathies Brain (IF 10.6) Pub Date : 2024-11-15 Gonzalo S Nido, Martina Castelli, Sepideh Mostafavi, Anna Rubiolo, Omnia Shadad, Guido Alves, Ole-Bjørn Tysnes, Christian Dölle, Charalampos Tzoulis
α-synucleinopathies are progressive neurodegenerative disorders characterized by intracellular aggregation of α-synuclein, yet their molecular pathogenesis remains unknow. Here, we explore cell-specific changes in gene expression across different α-synucleinopathies. We perform single-nucleus RNA sequencing on nearly 300,000 nuclei from the prefrontal cortex of individuals with idiopathic Parkinson’s
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Cognition and maps of injury in small vessel disease: time to move on from the black and white era Brain (IF 10.6) Pub Date : 2024-11-14 Michael O’Sullivan
This scientific commentary refers to ‘Enhancing cognitive performance prediction by white matter hyperintensity connectivity assessment’ by Petersen et al. (https://doi.org/10.1093/brain/awae315).
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Reduced brain oxygen response to spreading depolarization predicts worse outcome in ischaemic stroke Brain (IF 10.6) Pub Date : 2024-11-14 Nils Hecht, Daisy Haddad, Konrad Neumann, Leonie Schumm, Nora F Dengler, Lars Wessels, Patrick Dömer, Simeon Helgers, Franziska Meinert, Sebastian Major, Coline L Lemale, Jens P Dreier, Peter Vajkoczy, Johannes Woitzik
Spreading depolarization (SD) describes a propagating neuronal mass depolarization within the cerebral cortex that represents a mediator of infarct development and strongly stimulates the metabolic rate of O2 consumption. Here, we investigated the influence of Spreading Depolarization (SD) on brain tissue partial pressure of O2 (ptiO2) within the peri-infarct tissue of patients suffering malignant
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ATP1A3 dysfunction causes motor hyperexcitability and afterhyperpolarization loss in a dystonia model Brain (IF 10.6) Pub Date : 2024-11-13 Evgeny E Akkuratov, Francesca Sorrell, Laurence Picton, Vasco C Sousa, Martin Paucar, Daniel Jans, Lill-Britt Svensson, Maria Lindskog, Nicolas Fritz, Thomas Liebmann, Keith T Sillar, Hendrik Rosewich, Per Svenningsson, Hjalmar Brismar, Gareth B Miles, Anita Aperia
Mutations in the gene encoding the alpha3 Na+/K+-ATPase isoform (ATP1A3) lead to movement disorders that manifest with dystonia, a common neurological symptom with many different origins, but for which the underlying molecular mechanisms remain poorly understood. We have generated an ATP1A3 mutant mouse that displays motor impairments and a hyperexcitable motor phenotype compatible with dystonia. We
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Bridging the gaps between JCV infection models and human disease Brain (IF 10.6) Pub Date : 2024-11-13 Irene Cortese, C Sabrina Tan
This scientific commentary refers to ‘JC virus spread is potentiated by glial replication and demyelination-linked glial proliferation’ by Li et al. (https://doi.org/10.1093/brain/awae252).
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Soluble TREM2 distinguishes neuromyelitis optica spectrum disorder from MOG antibody disease. Brain (IF 10.6) Pub Date : 2024-11-12 Omar Chuquisana,Marianna Spatola,Alessandro Dinoto,María Sepúlveda,Sara Mariotto,Mar Tintore,Xavier Montalban,Manuel Comabella,Jan D Lünemann
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Current state and perspectives of CAR T cell therapy in central nervous system diseases Brain (IF 10.6) Pub Date : 2024-11-12 Lena Kristina Pfeffer, Felix Fischbach, Christoph Heesen, Manuel A Friese
B cell-directed CAR T cell therapy has fundamentally changed the treatment of hematological malignancies and its scope of application is rapidly expanding to include other diseases such as solid tumors or autoimmune disorders. Therapy-refractoriness remains an important challenge in various inflammatory and non-inflammatory disorders of the CNS. The reasons for therapy failure are diverse and include
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Shared orbitofrontal dynamics to a drug-themed movie track craving and recovery in heroin addiction Brain (IF 10.6) Pub Date : 2024-11-12 Greg Kronberg, Ahmet O Ceceli, Yuefeng Huang, Pierre-Olivier Gaudreault, Sarah G King, Natalie McClain, Nelly Alia-Klein, Rita Z Goldstein
Movies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-themed movie, where cues for drugs and other stimuli share
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HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model Brain (IF 10.6) Pub Date : 2024-11-12 Lein N H Dofash, Lee B Miles, Yoshihiko Saito, Eloy Rivas, Vanessa Calcinotto, Sara Oveissi, Rita J Serrano, Rachel Templin, Georg Ramm, Alison Rodger, Joel Haywood, Evan Ingley, Joshua S Clayton, Rhonda L Taylor, Chiara L Folland, David Groth, Daniella H Hock, David A Stroud, Svetlana Gorokhova, Sandra Donkervoort, Carsten G Bönnemann, Malika Sud, Grace E VanNoy, Brian E Mangilog, Lynn Pais, Anne
Rigid spine syndrome is a rare childhood-onset myopathy characterised by slowly progressive or non-progressive scoliosis, neck and spine contractures, hypotonia, and respiratory insufficiency. Biallelic variants in SELENON account for most cases of rigid spine syndrome, however, the underlying genetic cause in some patients remains unexplained. We used exome and genome sequencing to investigate the
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Patterns of tau, amyloid and synuclein pathology in ageing, Alzheimer’s disease and synucleinopathies Brain (IF 10.6) Pub Date : 2024-11-12 Sean J Colloby, Kirsty E McAleese, Lauren Walker, Daniel Erskine, Jon B Toledo, Paul C Donaghy, Ian G McKeith, Alan J Thomas, Johannes Attems, John-Paul Taylor
Alzheimer’s disease (AD) is neuropathologically defined by deposits of misfolded hyperphosphorylated tau (HP-tau) and β-amyloid. Lewy body (LB) dementia, which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is characterised pathologically by α-synuclein aggregates. HP-tau and β-amyloid can also occur as copathologies in LB dementia, and a diagnosis mixedAD/DLB can
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Multicentre analysis of seizure outcome predicted by removal of high frequency oscillations Brain (IF 10.6) Pub Date : 2024-11-12 Vasileios Dimakopoulos, Jean Gotman, Petr Klimes, Nicolas von Ellenrieder, Shi Bei Tan, Garnett Smith, Stephen Gliske, Margarita Maltseva, Minette Krisel Manalo, Martin Pail, Milan Brazdil, Dorien van Blooijs, Maryse van ‘t Klooster, Sarah Johnson, Samantha Laboy, Debora Ledergerber, Lukas Imbach, Christos Papadelis, Michael R Sperling, Maeike Zijlmans, Jan Cimbalnik, Julia Jacobs, William C Stacey
In drug-resistant focal epilepsy, planning surgical resection may involve presurgical intracranial EEG recordings (iEEG) to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. Eight international epilepsy centres recorded iEEG
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Exploiting blood-based biomarkers to align preclinical models with human traumatic brain injury. Brain (IF 10.6) Pub Date : 2024-11-09 Ilaria Lisi,Federico Moro,Edoardo Mazzone,Niklas Marklund,Francesca Pischiutta,Firas Kobeissy,Xiang Mao,Frances Corrigan,Adel Helmy,Fatima Nasrallah,Valentina Di Pietro,Laura B Ngwenya,Luis V Portela,Bridgette D Semple,Andrea L C Schneider,Ramon Diaz Arrastia,David K Menon,Douglas H Smith,Cheryl Wellington,David J Loane,Kevin Wang,Elisa R Zanier,
Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%. While there are several potential explanations for this, previous clinical trials have relied
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Metformin may reduce Alzheimer's disease risk by increasing soluble amyloid-β42 levels. Brain (IF 10.6) Pub Date : 2024-11-08 Timothy Daly,Bruno P Imbimbo
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Bridging the gap: unlocking the potential of emerging drug therapies for brain metastasis Brain (IF 10.6) Pub Date : 2024-11-08 Jiatong Ding, Yale Jiang, Ning Jiang, Shujun Xing, Fan Ge, Peiwen Ma, Qiyu Tang, Huilei Miao, Jiawei Zhou, Yuan Fang, Dandan Cui, Dongyan Liu, Yanjie Han, Weijie Yu, Yuning Wang, Guo Zhao, Yuanting Cai, Shuhang Wang, Nan Sun, Ning Li
Brain metastasis (BrM) remains an unmet clinical need in advanced cancers with an increasing incidence and poor prognosis. The limited response to various treatments is mainly derived from the presence of the substantive barrier, blood–brain barrier (BBB) and brain–tumor barrier (BTB), which hinders the access of potentially effective therapeutics to the metastatic tumor of brain. Recently, the understanding
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Mitochondrial dynamics and bioenergetics in Alzheimer’s induced pluripotent stem cell-derived neurons Brain (IF 10.6) Pub Date : 2024-11-08 Courtney MacMullen, Neelam Sharma, Ronald L Davis
Mitochondrial (MT) dysfunction is a hallmark of Alzheimer’s Disease (AD), but the scope and severity of these specific deficits across forms of AD are not well characterized. We designed a high-throughput, longitudinal, phenotypic assay to track MT dynamics and bioenergetics in glutamatergic iPSC-derived human neurons possessing mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2) and the amyloid
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Astroglial reactivity is a key modulator of Alzheimer’s disease pathological progression Brain (IF 10.6) Pub Date : 2024-11-08 Wiesje Pelkmans, Juan Domingo Gispert
This scientific commentary refers to ‘Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline’ by Peretti et al. (https://doi.org/10.1093/brain/awae211).
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Perivascular space dysfunction in cerebral small vessel disease is related to neuroinflammation Brain (IF 10.6) Pub Date : 2024-11-07 Hui Hong, Dan Tozer, Yutong Chen, Robin Brown, Audrey Low, Hugh S Markus
Enlarged perivascular spaces are a feature of cerebral small vessel disease, and it has been hypothesized that they may reflect impaired glymphatic drainage. The mechanisms underlying perivascular spaces enlargement are not fully understood, but both increased inflammation and blood brain barrier permeability have been hypothesized to play a role. We investigated the relationship between perivascular
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Mental health disorders before, during and after the COVID-19 pandemic: a nationwide study Brain (IF 10.6) Pub Date : 2024-11-06 Clara S Grønkjær, Rune H B Christensen, Daniel Kondziella, Michael E Benros
The COVID-19 pandemic and lockdowns prompted a major concern for mental health effects. Comprehensive nationwide studies are lacking on the indirect effect of the COVID-19 pandemic on the population’s mental health. We aimed to determine whether the COVID-19 pandemic and lockdowns affected mental health service usage, suicide attempts, and suicides. This comprehensive nationwide register-linked study
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Tau, synapse loss and gliosis progress in an Alzheimer’s mouse model after amyloid-β immunotherapy Brain (IF 10.6) Pub Date : 2024-11-06 Lindsay A Welikovitch, Anastasie Mate de Gerando, Anita Khasnavis, Harshil Bhavsar, Jonah C Meltzer, Luc Buée, Lori B Chibnik, Thierry Bussiere, Bradley T Hyman
While preclinical studies assessing drugs for Alzheimer’s disease (AD) are conducted in animal models that usually display only one neuropathological feature of AD, patients present with a complex combination of comorbidities and neuropathologies. Importantly, it is well-established that amyloid (Aβ) plaque and tau tangle accumulation interact in a phase-dependent manner, making it difficult to predict
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Focal brain administration of antiseizure medications improves outcomes and reduces side effects. Brain (IF 10.6) Pub Date : 2024-11-06 Annamaria Vezzani
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Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation. Brain (IF 10.6) Pub Date : 2024-11-06 Jan Smeitink,Just van Es,Brigitte Bosman,Mirian C H Janssen,Thomas Klopstock,Grainne Gorman,John Vissing,Gerrit Ruiterkamp,Chris J Edgar,Evertine J Abbink,Rob van Maanen,Oksana Pogoryelova,Claudia Stendel,Almut Bischoff,Ivan Karin,Mahtab Munshi,Anne Kümmel,Lydia Burgert,Christianne Verhaak,Herma Renkema
Mitochondrial disease is a group of rare conditions, with no approved treatment to date, except for Leber hereditary optic neuropathy. Therapeutic options to alleviate the symptoms of mitochondrial disease are urgently needed. Sonlicromanol is a promising candidate, as it positively alters the key metabolic and inflammatory pathways associated with mitochondrial disease. Sonlicromanol is a reductive
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Smaller cingulate grey matter mediates the association between dual-task gait and incident dementia Brain (IF 10.6) Pub Date : 2024-11-05 Pauline Ali, Frederico Pieruccini-Faria, Cédric Annweiler, Mickaël Dinomais, Surim Son, Scott K Wilson, Richard Camicioli, Susan Muir-Hunter, Robert Bartha, Manuel Montero-Odasso
Individuals with mild cognitive impairment that have high dual-task gait cost (≥20% slowing in gait speed while performing a cognitive brain demanding task), are three-fold more likely to progress to dementia. However, the cortical regions that may explain this association are unknown, which may identify potentially treatable areas. The aim of the current study is to investigate whether brain grey
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Natural history of Becker muscular dystrophy: DMD gene mutations predict clinical severity Brain (IF 10.6) Pub Date : 2024-11-05 Domenico Gorgoglione, Daniele Sabbatini, Pietro Riguzzi, Giuliana Capece, Marika Pane, Serenella Servidei, Marta Briganti, Cristina Sancricca, Fabio Bruschi, Anna Ardissone, Riccardo Masson, Annamaria Gallone, Lorenzo Maggi, Esther Picillo, Luisa Politano, Angela Petrosino, Sara Vianello, Martina Penzo, Matteo Villa, Maria Sframeli, Cosimo Allegra, Andrea Barp, Alessandra Di Bari, Francesca Salmin
Background Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease due to mutations in the DMD gene, leading to a deficient and less functional dystrophin mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments. Materials and methods Retrospective data were collected from 943 patients diagnosed
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The Parkinson's disease DJ-1/PARK7 gene controls peripheral neuronal excitability and painful neuropathy Brain (IF 10.6) Pub Date : 2024-11-01 Sang Hoon Lee, Raquel Tonello, Kihwan Lee, Jueun Roh, Arthur Silveira Prudente, Yong Ho Kim, Chul-Kyu Park, Temugin Berta
Parkinson's disease is a progressive neurodegenerative disease with well-documented motor symptoms as well as less recognised, but significant, non-motor symptoms. These non-motor symptoms include prodromal pain and peripheral neuropathy, the causes of which are unknown. We investigated the role of DJ-1/PARK7, a Parkinson's disease-associated gene, in prodromal pain and peripheral neuropathy. Using
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Nifuroxazide rescues the deleterious effects due to CHCHD10-associated MICOS defects in disease models Brain (IF 10.6) Pub Date : 2024-10-31 Baptiste Ropert, Sylvie Bannwarth, Emmanuelle C Genin, Loan Vaillant-Beuchot, Sandra Lacas-Gervais, Blandine Madji Hounoum, Aurore Bernardin, Nhu Dinh, Alessandra Mauri-Crouzet, Marc-Alexandre D’Elia, Gaelle Augé, Françoise Lespinasse, Audrey Di Giorgio, Willian Meira, Nathalie Bonnefoy, Laurent Monassier, Manuel Schiff, Laila Sago, Devrim Kilinc, Frédéric Brau, Virginie Redeker, Delphine Bohl, Déborah
The identification of a point mutation (p.Ser59Leu) in the CHCHD10 gene was the first genetic evidence that mitochondrial dysfunction can trigger motor neuron disease. Since then, we have shown that this mutation leads to the disorganization of the MItochondrial contact site and Cristae Organizing System (MICOS) complex that maintains the mitochondrial cristae structure. Here, we generated yeast mutant
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AAV-based TCAP delivery rescues mitochondria dislocation in limb-girdle muscular dystrophy R7 Brain (IF 10.6) Pub Date : 2024-10-29 Xiaoqing Lv, Shuangwu Liu, Xi Li, He Lv, Kai Shao, Sushan Luo, Dandan Zhao, Chuanzhu Yan, Pengfei Lin
Limb-girdle muscular dystrophy R7 is a rare genetic disease caused by homozygous or compound heterozygous variants in the titin-cap (TCAP) gene that results in the absence of the protein telethonin. The primary pathological features of limb-girdle muscular dystrophy R7 are fiber size variation, nuclear centralization, and abnormal mitochondrial distribution. The mechanisms underlying this disease are
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Supraspinal contributions to defective antagonistic inhibition and freezing of gait in Parkinson’s disease Brain (IF 10.6) Pub Date : 2024-10-29 Philipp Klocke, Moritz A Loeffler, Hannah Muessler, Maria-Sophie Breu, Alireza Gharabaghi, Daniel Weiss
The neuromuscular circuit mechanisms of freezing of gait in Parkinson’s disease have received little study. Technological progress enables researchers chronically to sense local field potential activity of the basal ganglia in patients while walking. To study subthalamic activity and the circuit processes of supraspinal contributions to spinal motor integration, we recorded local field potentials,
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Correction to: Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations. Brain (IF 10.6) Pub Date : 2024-10-28
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A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests Brain (IF 10.6) Pub Date : 2024-10-26 Noëlle Warmenhoven, Gemma Salvadó, Shorena Janelidze, Niklas Mattsson-Carlgren, Divya Bali, Anna Orduña Dolado, Hartmuth Kolb, Gallen Triana-Baltzer, Nicolas R Barthélemy, Suzanne E Schindler, Andrew J Aschenbrenner, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Laura Ibanez, Jigyasha Timsina, Carlos Cruchaga, Randall J Bateman, Nicholas Ashton, Burak Arslan, Henrik Zetterberg, Kaj Blennow, Alexa
Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer’s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against
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CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability Brain (IF 10.6) Pub Date : 2024-10-26 Marina P Hommersom, Nina Doorn, Sofía Puvogel, Elly I Lewerissa, Annika Mordelt, Ummi Ciptasari, Franziska Kampshoff, Lieke Dillen, Ellen van Beusekom, Astrid Oudakker, Naoki Kogo, Amalia M Dolga, Monica Frega, Dirk Schubert, Bart P C van de Warrenburg, Nael Nadif Kasri, Hans van Bokhoven
Haploinsufficiency of the CACNA1A gene, encoding the pore-forming α1 subunit of P/Q-type voltage-gated calcium channels, is associated with a clinically variable phenotype ranging from cerebellar ataxia, to neurodevelopmental syndromes with epilepsy and intellectual disability. To understand the pathological mechanisms of CACNA1A loss-of-function variants, we characterized a human neuronal model for
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MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination Brain (IF 10.6) Pub Date : 2024-10-26 Charles Frison-Roche, Célia Martin Demier, Steve Cottin, Jeanne Lainé, Ludovic Arandel, Marius Halliez, Mégane Lemaitre, Xavière Lornage, Laure Strochlic, Maurice S Swanson, Cécile Martinat, Julien Messéant, Denis Furling, Frédérique Rau
Muscleblind-like proteins (MBNLs) are a family of RNA-binding proteins that play essential roles in the regulation of RNA metabolism. Beyond their canonical role in RNA regulation, MBNL proteins have emerged as key players in the pathogenesis of Myotonic Dystrophy type 1 (DM1). In DM1, sequestration of MBNL proteins by expansion of the CUG repeat RNA leads to functional depletion of MBNL, resulting
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Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts Brain (IF 10.6) Pub Date : 2024-10-24 Sophie N M Binks, Katherine S Elliott, Sergio Muñiz-Castrillo, Edmund Gilbert, Tânia Kawasaki de Araujo, Andrew R Harper, Andrew C Brown, Amanda Y Chong, Gavin Band, Vicente Peris Sempere, Anne-Laurie Pinto, Felicie Costantino, N William Rayner, Alexander J Mentzer, Norman Delanty, Veronique Rogemond, Géraldine Picard, Adam E Handel, Nico Melzer, Maarten J Titulaer, Soon-Tae Lee, Frank Leypoldt, Gregor
Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesised the presence
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CCL2 blockade combined with PD-1/P-selectin immunomodulators impedes breast cancer brain metastasis Brain (IF 10.6) Pub Date : 2024-10-24 Sahar Israeli Dangoor, Rami Khoury, Koren Salomon, Sabina Pozzi, Shir Shahar, Adan Miari, Yael Leichtmann-Bardoogo, Neta Bar-Hai, Neta Frommer, Eilam Yeini, Tom Winkler, Nora Balint Lahat, Iris Kamer, Ori Hadad, Kathrin Laue, Henry Brem, Thomas M Hyde, Jair Bar, Iris Barshack, Uri Ben-David, Dana Ishay-Ronen, Ben M Maoz, Ronit Satchi-Fainaro
Over the last two decades, the diagnosis and treatment of breast cancer patients have considerably improved. However, brain metastases remain a major clinical challenge and a leading cause of mortality. Thus, a better understanding of the pathways involved in the metastatic cascade is essential. To this end, we have investigated the reciprocal effects of astrocytes and breast cancer cells, employing
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Radiosurgery versus observation for brainstem cavernous malformations: a 5-year multicentre cohort study Brain (IF 10.6) Pub Date : 2024-10-24 Da Li, Jian-Cong Weng, Shi-Bin Sun, Gui-Jun Zhang, Bo-Han Yao, Guo-Kai Wang, Jing Chen, Shou-Xin Feng, Hai-Tao Liu, Fu-Gui Zhou, Pan-Pan Liu, Lu Kong, Hui Zhou, Hao-Yu Zhang, Xiao-Jun Zeng, Ze-Yu Wu, Jiu-Luan Lin, Cong Ren, Wei Wang, Hong-Jun Zhang, Xiao-Ying Xu, Lai-Rong Song, Xin Du, Liang Wang
The role of radiosurgery in preventing haemorrhage in brainstem cavernous malformations remains a subject of debate. This study aims to evaluate whether radiosurgery provides a protective benefit against haemorrhage in these patients. This multicentre, prospective observational study was conducted in 17 centres and enrolled eligible patients with brainstem cavernous malformations consecutively. Data
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Delineating three distinct spatiotemporal patterns of brain atrophy in Parkinson’s disease Brain (IF 10.6) Pub Date : 2024-10-24 Yusuke Sakato, Atsushi Shima, Yuta Terada, Kiyoaki Takeda, Haruhi Sakamaki-Tsukita, Akira Nishida, Kenji Yoshimura, Ikko Wada, Koji Furukawa, Daisuke Kambe, Hiroki Togo, Yohei Mukai, Masanori Sawamura, Etsuro Nakanishi, Hodaka Yamakado, Yasutaka Fushimi, Tomohisa Okada, Yuji Takahashi, Yuji Nakamoto, Ryosuke Takahashi, Takashi Hanakawa, Nobukatsu Sawamoto
The clinical manifestation of Parkinson’s disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson’s disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration
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Central nervous system manifestations in acute and chronic graft-versus-host disease. Brain (IF 10.6) Pub Date : 2024-10-23 Nicolas Lambert,Florence Forte,Majdouline El Moussaoui,Justine Monseur,Nicole Raus,Alexey Polushin,David Michonneau,Carl Shultz,William J Hogan,Aitana Balaguer-Roselló,Sara Gil-Perotìn,Jan Brijs,Paul Chauvet,Maria Gavriilaki,Martin Carre,Adriana Octaviana Dulamea,Yves Chalandon,Urpu Salmenniemi,Andrea Duminuco,Ron Ram,Irene García-Cadenas,Gaetana Porto,Stéphanie Nguyen,Portia Smallbone,Marta González-Vicent
Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible
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A long look at Copley’s A Boy with a Flying Squirrel: implications for the default mode network Brain (IF 10.6) Pub Date : 2024-10-23 Geoffrey D Schott
What happens in the brain when a person spends 3 hours viewing a single painting? Geoffrey Schott examines the account of an art history professor who did just that, and considers what their observations reveal about the differences between seeing and looking, and between looking and perceiving.
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α2δ-2 regulates synaptic GluK1 kainate receptors in Purkinje cells and motor coordination Brain (IF 10.6) Pub Date : 2024-10-23 Meng-Hua Zhou, Jing-Jing Zhou, Shao-Rui Chen, Hong Chen, Daozhong Jin, Yuying Huang, Jian-Ying Shao, Hui-Lin Pan
Gabapentin and pregabalin are inhibitory ligands of both α2δ-1 and α2δ-2 proteins (also known as subunits of voltage-activated Ca2+ channels) and are commonly prescribed for the treatment of neuropathic pain and epilepsy. However, these drugs can cause gait disorders and ataxia through unknown mechanisms. α2δ-2 and GluK1, a glutamate-gated kainate receptor subtype, are coexpressed in cerebellar Purkinje
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Methylphenidate differentially alters corticostriatal connectivity after traumatic brain injury Brain (IF 10.6) Pub Date : 2024-10-21 Emma-Jane Mallas, Sara De Simoni, Peter O Jenkins, Michael C B David, Niall J Bourke, David J Sharp
Traumatic brain injury commonly impairs attention and executive function, and disrupts the large-scale brain networks that support these cognitive functions. Abnormalities of functional connectivity are seen in corticostriatal networks, which are associated with executive dysfunction and damage to neuromodulatory catecholaminergic systems caused by head injury. Methylphenidate, a stimulant medication
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Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes Brain (IF 10.6) Pub Date : 2024-10-21 Adam Al-Diwani, Nicholas M Provine, Andrew Murchison, Rhiannon Laban, Owen J Swann, Ivan Koychev, Fintan Sheerin, Sandro Da Mesquita, Amanda Heslegrave, Henrik Zetterberg, Paul Klenerman, Sarosh R Irani
In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs), and this drainage function is reduced with ageing. If this occurred in humans, CLNs may provide a readily accessible measure of this aspect of protein clearance. We tested this hypothesis in people using ultrasound-guided fine needle aspiration (FNA). We measured amyloid-beta 40 and 42, phospho-Tau-181, gl
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Basal ganglia theta power indexes trait anxiety in people with Parkinson’s disease Brain (IF 10.6) Pub Date : 2024-10-21 Bart E K S Swinnen, Colin W Hoy, Elena Pegolo, Bryony Ishihara, Elena Ubeda Matzilevich, Julia Sun, Francesca Morgante, Erlick Pereira, Fahd Baig, Michael Hart, Huiling Tan, Zimi Sawacha, Martijn Beudel, Sarah Wang, Philip Starr, Simon Little, Lucia Ricciardi
Neuropsychiatric symptoms are common and disabling in Parkinson’s disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments. In this study, we assessed the intracranial neurophysiological correlates of anxiety
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Associations between accelerated forgetting, amyloid deposition and brain atrophy in older adults Brain (IF 10.6) Pub Date : 2024-10-18 Kirsty Lu, John Baker, Jennifer M Nicholas, Rebecca E Street, Sarah E Keuss, William Coath, Sarah-Naomi James, Ashvini Keshavan, Philip S J Weston, Heidi Murray-Smith, David M Cash, Ian B Malone, Andrew Wong, Nick C Fox, Marcus Richards, Sebastian J Crutch, Jonathan M Schott
Accelerated long-term forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer’s disease pathology, and how memory selectivity may influence which material is
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Lesion and lesion network localization of dysnomia after epilepsy surgery Brain (IF 10.6) Pub Date : 2024-10-17 Asmaa Mhanna, Joel Bruss, Joseph C Griffis, Alyssa W Sullivan, Hiroto Kawasaki, Jeffrey Binder, Sara B Pillay, Matthew A Howard, Daniel Tranel, Aaron D Boes
Temporal lobe (TL) epilepsy surgery is an effective treatment option for patients with drug-resistant epilepsy. However, neurosurgery poses a risk for cognitive deficits - up to one third of patients have a decline in naming ability following TL surgery. In this study, we aimed to better understand the neural correlates associated with reduced naming performance after TL surgery, with the goal of informing
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Clinical and genetic landscape of optic atrophy in 826 families: insights from 50 nuclear genes Brain (IF 10.6) Pub Date : 2024-10-17 Yuxi Zheng, Panfeng Wang, Shiqiang Li, Yuxi Long, Yi Jiang, Dongwei Guo, Xiaoyun Jia, Mengchu Liu, Yiyan Zeng, Xueshan Xiao, J Fielding Hejtmancik, Qingjiong Zhang, Wenmin Sun
Hereditary optic neuropathies (HON) are a group of diseases due to genetic defects either in mitochondria or in nuclear genomes. The increasing availability of genetic testing has expanded a broader genetic and phenotypic spectrum of HON than previously recognized. To provide systematic insight into the genetic and phenotypic landscape of HON attributed to 50 nuclear genes, we conducted genetic analysis
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Amyloid-β predominant Alzheimer's disease neuropathologic change. Brain (IF 10.6) Pub Date : 2024-10-17 Gabor G Kovacs,Yuriko Katsumata,Xian Wu,Khine Zin Aung,David W Fardo,Shelley L Forrest,,Peter T Nelson
Different subsets of Alzheimer's disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread Aβ plaques but no/mild tau tangles (Aβ-predominant ADNC, or AP-ADNC), may have distinct genetic and clinical features. Analyzing National Alzheimer's Coordinating Center data, we stratified 1,187 participants into AP-ADNC (n = 95), low Braak primary age related
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Motor compensation in Parkinson’s disease: an empirical challenge with clinical implications Brain (IF 10.6) Pub Date : 2024-10-17 Bénédicte Ballanger, Philippe Boulinguez
This scientific commentary refers to ‘Neurophysiological markers of motor compensatory mechanisms in early Parkinson’s disease’ by Passaretti et al. (https://doi.org/10.1093/brain/awae210).
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Default mode network tau predicts future clinical decline in atypical early Alzheimer’s disease Brain (IF 10.6) Pub Date : 2024-10-16 Yuta Katsumi, Inola A Howe, Ryan Eckbo, Bonnie Wong, Megan Quimby, Daisy Hochberg, Scott M McGinnis, Deepti Putcha, David A Wolk, Alexandra Touroutoglou, Bradford C Dickerson
Identifying individuals with early-stage Alzheimer’s disease (AD) at greater risk of steeper clinical decline would enable better-informed medical, support, and life planning decisions. Despite accumulating evidence on the clinical prognostic value of tau positron emission tomography (PET) in typical late-onset amnestic AD, its utility in predicting clinical decline in individuals with atypical forms