-
Cholinergic innervation topography in GBA-associated de novo Parkinson’s disease patients Brain (IF 14.5) Pub Date : 2023-09-25 Sofie Slingerland, Sygrid van der Zee, Giulia Carli, Anne C Slomp, Jeffrey M Boertien, Emile d’Angremont, Nicolaas I Bohnen, Roger L Albin, Teus van Laar
The most common genetic risk factors for Parkinson’s disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with GBA1 mutations (GBA-PD) exhibit earlier age of onset and faster disease progression with more severe cognitive impairments, postural instability, and gait problems. These GBA-PD features suggest more severe cholinergic system pathologies. PET imaging with
-
Brain MRI research in neurodegenerative dementia: time to deliver on promises Brain (IF 14.5) Pub Date : 2023-09-22 Simon Ducharme
This scientific commentary refers to ‘Atrophy in behavioural variant frontotemporal dementia spans multiple large-scale prefrontal and temporal networks’ by Eldaief et al. (https://doi.org/10.1093/brain/awad167).
-
Soluble TREM2 triggers microglial dysfunction in neuromyelitis optica spectrum disorders Brain (IF 14.5) Pub Date : 2023-09-22 Chuan Qin, Man Chen, Ming-Hao Dong, Sheng Yang, Hang Zhang, Yun-Fan You, Luo-Qi Zhou, Yun-Hui Chu, Yue Tang, Xiao-Wei Pang, Long-Jun Wu, Dai-Shi Tian, Wei Wang
Microglia-mediated neuroinflammation contributes to acute demyelination in neuromyelitis optica spectrum disorders (NMOSD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in the cerebrospinal fluid (CSF) has been associated with microglial activation in several neurodegenerative diseases. However, the basis for this immune-mediated attack and the pathophysiological role of sTREM2
-
Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort Brain (IF 14.5) Pub Date : 2023-09-18 Kiran Polavarapu, Balaraju Sunitha, Ana Töpf, Veeramani Preethish-kumar, Rachel Thompson, Seena Vengalil, Saraswati Nashi, Mainak Bardhan, Sai Bhargava Sanka, Akshata Huddar, Gopikrishnan Unnikrishnan, Gautham Arunachal, Manu Santhappan Girija, Anna Porter, Yoshiteru Azuma, Paulo José Lorenzoni, Dipti Baskar, Ram Murthy Anjanappa, Madassu Keertipriya, Hansashree Padmanabh, Ganaraja Valakunja Harikrishna
Congenital myasthenic syndromes are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and beta2 adrenergic receptor agonists. In this study we identify and genetically characterise the largest cohort of congenital myasthenic syndrome patients from
-
Grey matter heterotopia subtypes show specific morpho-electric signatures and network dynamics Brain (IF 14.5) Pub Date : 2023-09-18 Jean-Christophe Vermoyal, Delphine Hardy, Lucas Goirand-Lopez, Antonin Vinck, Lucas Silvagnoli, Aurélien Fortoul, Fiona Francis, Silvia Cappello, Ingrid Bureau, Alfonso Represa, Carlos Cardoso, Françoise Watrin, Thomas Marissal, Jean-Bernard Manent
Grey matter heterotopia (GMH) are neurodevelopmental disorders associated with abnormal cortical function and epilepsy. Subcortical band heterotopia (SBH) and periventricular nodular heterotopia (PVNH) are two well-recognized GMH subtypes in which neurons are misplaced, either forming nodules lining the ventricles in PVNH, or forming bands in the white matter in SBH. Although both PVNH and SBH are
-
Gut microbiome correlates with plasma lipids in amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2023-09-18 Kai Guo, Claudia Figueroa-Romero, Mohamed H Noureldein, Benjamin J Murdock, Masha G Savelieff, Junguk Hur, Stephen A Goutman, Eva L Feldman
Amyotrophic lateral sclerosis (ALS) is a complex, fatal neurodegenerative disease. Disease pathophysiology is incompletely understood, but evidence suggests gut dysbiosis occurs in ALS, linked to impaired gastrointestinal integrity, immune system dysregulation, and altered metabolism. Gut microbiome and plasma metabolome have been separately investigated in ALS, but little is known about gut microbe-plasma
-
Interactions between vascular burden and amyloid-β pathology on trajectories of tau accumulation Brain (IF 14.5) Pub Date : 2023-09-17 Emma M Coomans, Danielle van Westen, Alexa Pichet Binette, Olof Strandberg, Nicola Spotorno, Geidy E Serrano, Thomas G Beach, Sebastian Palmqvist, Erik Stomrud, Rik Ossenkoppele, Oskar Hansson
Cerebrovascular pathology often co-exists with Alzheimer’s disease pathology and can contribute to Alzheimer’s disease-related clinical progression. However, the degree to which vascular burden contributes to Alzheimer’s disease pathological progression is still unclear. This study aimed to investigate interactions between vascular burden and amyloid-β pathology on both baseline tau tangle load and
-
The parietal architecture binding cognition to sensorimotor integration: a multimodal causal study Brain (IF 14.5) Pub Date : 2023-09-15 Luca Fornia, Antonella Leonetti, Guglielmo Puglisi, Marco Rossi, Luca Viganò, Bianca Della Santa, Luciano Simone, Lorenzo Bello, Gabriella Cerri
Despite human’s praxis abilities are unique among primates, comparative observations suggest that these cognitive motor skills could have emerged from exploitation and adaptation of phylogenetically older building blocks, namely the parieto-frontal networks sub-serving prehension and manipulation. Within this framework, investigating to which extent praxis and prehension-manipulation overlap and diverge
-
TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions Brain (IF 14.5) Pub Date : 2023-09-13 Hashem Almousa, Sara A Lewis, Somayeh Bakhtiari, Sandra Hinz Nordlie, Alex Pagnozzi, Helen Magee, Stephanie Efthymiou, Jennifer A Heim, Patricia Cornejo, Maha S Zaki, Najwa Anwar, Shazia Maqbool, Fatima Rahman, Derek E Neilson, Anusha Vemuri, Sheng Chih Jin, Xiao-Ru Yang, Abolfazl Heidari, Koen van Gassen, Aurélien Trimouille, Christel Thauvin-Robinet, James Liu, Ange-Line Bruel, Hoda Tomoum, Mennatallah
Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand
-
A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex Brain (IF 14.5) Pub Date : 2023-09-13 Andrea I Luppi, Manesh Girn, Fernando E Rosas, Christopher Timmermann, Leor Roseman, David Erritzoe, David J Nutt, Emmanuel A Stamatakis, R Nathan Spreng, Lei Xing, Wieland B Huttner, Robin L Carhart-Harris
Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signaling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the
-
White matter tracts and executive functions: a review of causal and correlation evidence Brain (IF 14.5) Pub Date : 2023-09-13 Monica Ribeiro, Yordanka Nikolova Yordanova, Vincent Noblet, Guillaume Herbet, Damien Ricard
Executive functions are high-level cognitive processes involving abilities such as working memory/updating, set-shifting and inhibition. These complex cognitive functions are enabled by interactions among widely distributed cognitive networks, supported by white matter tracts. Executive impairment is frequent in neurological conditions affecting white matter; however, whether specific tracts are crucial
-
Trazodone rescues dysregulated synaptic and mitochondrial nascent proteomes in prion neurodegeneration Brain (IF 14.5) Pub Date : 2023-09-13 Hector Albert-Gasco, Heather L Smith, Beatriz Alvarez-Castelao, Dean Swinden, Mark Halliday, Sudha Janaki-Raman, Adrian Butcher, Giovanna R Mallucci
The unfolded protein response (UPR) is rapidly gaining momentum as a therapeutic target for protein misfolding neurodegenerative diseases, in which its overactivation results in sustained translational repression leading to synapse loss and neurodegeneration. In mouse models of these disorders, from Alzheimer’s to prion disease, modulation of the pathway - including by the licensed drug, trazodone
-
Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy Brain (IF 14.5) Pub Date : 2023-09-11 Richard J L F Lemmers, Russell Butterfield, Patrick J van der Vliet, Jan L de Bleecker, Ludo van der Pol, Diane M Dunn, Corrie E Erasmus, Marc D'Hooghe, Kristof Verhoeven, Judit Balog, Anne Bigot, Baziel van Engelen, Jeffrey Statland, Enrico Bugiardini, Nienke van der Stoep, Teresinha Evangelista, Chiara Marini-Bettolo, Peter van den Bergh, Rabi Tawil, Nicol C Voermans, John Vissing, Robert B Weiss
Facioscapulohumeral dystrophy (FSHD) has a unique genetic etiology resulting in partial chromatin relaxation of the D4Z4 macrosatellite repeat array on 4qter. This D4Z4 chromatin relaxation facilitates inappropriate expression of the transcription factor DUX4 in skeletal muscle. DUX4 is encoded by a retrogene which is embedded within the distal region of the D4Z4 repeat array. In the European population
-
Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology Brain (IF 14.5) Pub Date : 2023-09-10 Iain J Hartnell, Declan Woodhouse, William Jasper, Luke Mason, Pavan Marwaha, Manon Graffeuil, Laurie C Lau, Jeanette L Norman, David S Chatelet, Luc Buee, James A R Nicoll, David Blum, Guillaume Dorothee, Delphine Boche
Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of frontotemporal lobar degeneration (FTLD) cases. Identification of genetic risk variants related to innate/adaptive immunity have highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Studies have shown microglial and astrocyte activation together with T cell infiltration in
-
Brain perivascular macrophages: current understanding and future prospects Brain (IF 14.5) Pub Date : 2023-09-09 Wenjie Wen, Jinping Cheng, Yamei Tang
Brain perivascular macrophages are specialized populations of macrophages that reside in the space around cerebral vessels, such as penetrating arteries and venules. With the help of cutting-edge technologies such as cell fate mapping and single-cell multi-omics, their multifaceted, pivotal roles in phagocytosis, antigen presentation, vascular integrity maintenance, and metabolic regulation have more
-
Can immunological imprinting drive neurological dysfunction in long COVID? Brain (IF 14.5) Pub Date : 2023-09-08 Dennis L Kolson
This scientific commentary refers to ‘Neurologic sequelae of COVID-19 are determined by immunologic imprinting from previous coronaviruses’ by Spatola et al. (https://doi.org/10.1093/brain/awad155).
-
Abnormal higher-order network interactions in Parkinson’s disease visual hallucinations Brain (IF 14.5) Pub Date : 2023-09-07 Joshua B Tan, Eli J Müller, Isabella F Orlando, Natasha L Taylor, Daniel S Margulies, Jennifer Szeto, Simon J G Lewis, James M Shine, Claire O’Callaghan
Visual hallucinations in Parkinson’s disease can be viewed from a systems-level perspective, whereby dysfunctional communication between brain networks responsible for perception predisposes a person to hallucinate. To this end, abnormal functional interactions between higher-order and primary sensory networks have been implicated in the pathophysiology of visual hallucinations in Parkinson’s disease
-
On-demand low-frequency stimulation for seizure control: efficacy and behavioural implications Brain (IF 14.5) Pub Date : 2023-09-07 Enya Paschen, Piret Kleis, Diego M Vieira, Katharina Heining, Christian Boehler, Ulrich Egert, Ute Häussler, Carola A Haas
Mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulation at high frequencies is applied to interrupt ongoing
-
Pleiotropy with sex-specific traits reveals genetic aspects of sex differences in Parkinson’s disease Brain (IF 14.5) Pub Date : 2023-09-06 Kaja Nordengen, Chiara Cappelletti, Shahram Bahrami, Oleksandr Frei, Lasse Pihlstrøm, Sandra Pilar Henriksen, Hanneke Geut, Annemieke J M Rozemuller, Wilma D J van de Berg, Ole A Andreassen, Mathias Toft
Parkinson’s disease is an age-related neurodegenerative disorder with a higher incidence in males than females. The causes for this sex difference are unknown. Genome-wide association studies (GWAS) have identified 90 Parkinson’s disease risk loci, but the genetic studies have not found sex-specific differences in allele frequency on autosomal chromosomes or sex chromosomes. Genetic variants, however
-
Distal hereditary motor neuropathy caused by coenzyme Q deficiency due to COQ7 variants Brain (IF 14.5) Pub Date : 2023-09-05 Maria Andrea Desbats, Leonardo Salviati
This scientific commentary refers to ‘Biallelic variants in COQ7 cause distal hereditary motor neuropathy with upper motor neuron signs’ by Rebelo et al. (https://doi.org/10.1093/brain/awad158).
-
Neuromelanin-sensitive MRI as a promising biomarker of catecholamine function Brain (IF 14.5) Pub Date : 2023-09-05 Paula Trujillo, Megan A Aumann, Daniel O Claassen
Disruptions to dopamine and noradrenergic neurotransmission are noted in several neurodegenerative and psychiatric disorders. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) offers a non-invasive approach to visualize and quantify the structural and functional integrity of the substantia nigra and locus coeruleus. This method may aid in the diagnosis and quantification of longitudinal changes
-
Cross-seeding by prion protein inactivates TDP-43 Brain (IF 14.5) Pub Date : 2023-09-05 Stella A Polido, Cristiana Stuani, Aaron Voigt, Papiya Banik, Janine Kamps, Verian Bader, Prerna Grover, Laura J Krause, Inga Zerr, Jakob Matschke, Markus Glatzel, Konstanze F Winklhofer, Emanuele Buratti, Jörg Tatzelt
A common pathological denominator of various neurodegenerative diseases is the accumulation of protein aggregates. Neurotoxic effects are caused by a loss of the physiological activity of the aggregating protein and/or a gain of toxic function of the misfolded protein conformers. In transmissible spongiform encephalopathies or prion diseases, neurodegeneration is caused by aberrantly folded isoforms
-
Brain tumour genetic network signatures of survival Brain (IF 14.5) Pub Date : 2023-09-04 James K Ruffle, Samia Mohinta, Guilherme Pombo, Robert Gray, Valeriya Kopanitsa, Faith Lee, Sebastian Brandner, Harpreet Hyare, Parashkev Nachev
Tumour heterogeneity is increasingly recognized as a major obstacle to therapeutic success across neuro-oncology. Gliomas are characterized by distinct combinations of genetic and epigenetic alterations, resulting in complex interactions across multiple molecular pathways. Predicting disease evolution and prescribing individually optimal treatment requires statistical models complex enough to capture
-
Impaired glucose utilization in the brain of patients with delirium following hip fracture Brain (IF 14.5) Pub Date : 2023-09-01 Irit Titlestad, Leiv Otto Watne, Gideon A Caplan, Adrian McCann, Per Magne Ueland, Bjørn Erik Neerland, Marius Myrstad, Nathalie Bodd Halaas, Christian Thomas Pollmann, Kristi Henjum, Anette Hylen Ranhoff, Lene B Solberg, Wender Figved, Colm Cunningham, Lasse M Giil
Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there is limited data on metabolic alterations found in CSF samples, and targeted
-
Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity Brain (IF 14.5) Pub Date : 2023-09-01 Jakob Hakon, Miriana J Quattromani, Carin Sjölund, Daniela Talhada, Bungchan Kim, Slavianka Moyanova, Federica Mastroiacovo, Luisa Di Menna, Roger Olsson, Elisabet Englund, Ferdinando Nicoletti, Karsten Ruscher, Adam Q Bauer, Tadeusz Wieloch
Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections
-
The Capgras syndrome Brain (IF 14.5) Pub Date : 2023-08-30 Alan Carson
One hundred years ago, Joseph Capgras published the first description of the disorder of delusional misidentification that now bears his name. Alan Carson marks the centenary of that publication by reflecting on Capgras and his eponymous syndrome.
-
SLC6A1 variant pathogenicity, molecular function, and phenotype: a genetic and clinical analysis Brain (IF 14.5) Pub Date : 2023-08-30 Arthur Stefanski, Eduardo Pérez-Palma, Tobias Brünger, Ludovica Montanucci, Cornelius Gati, Chiara Klöckner, Katrine M Johannesen, Kimberly Goodspeed, Marie Macnee, Alexander T Deng, Ángel Aledo-Serrano, Artem Borovikov, Maina Kava, Arjan M Bouman, M J Hajianpour, Deb K Pal, Marc Engelen, Eveline E O Hagebeuk, Marwan Shinawi, Alexis R Heidlebaugh, Kathryn Oetjens, Trevor L Hoffman, Pasquale Striano
Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants
-
Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity Brain (IF 14.5) Pub Date : 2023-08-29 Susan X N Lin, Philip K Ahring, Angelo Keramidas, Vivian W Y Liao, Rikke S Møller, Mary Chebib, Nathan L Absalom
Genetic variants associated with developmental and epileptic encephalopathies have been identified in the GABRB3 gene that encodes the β3 subunit of GABAA receptors. Typically, variants alter receptor sensitivity to GABA resulting in either gain- or loss-of-function, which correlates with patient phenotypes. However, it is unclear how another important receptor property, desensitization, contributes
-
Prognostic value of single-subject grey matter networks in early multiple sclerosis Brain (IF 14.5) Pub Date : 2023-08-29 Vinzenz Fleischer, Gabriel Gonzalez-Escamilla, Deborah Pareto, Alex Rovira, Jaume Sastre-Garriga, Piotr Sowa, Einar A Høgestøl, Hanne F Harbo, Barbara Bellenberg, Carsten Lukas, Serena Ruggieri, Claudio Gasperini, Tomas Uher, Manuela Vaneckova, Stefan Bittner, Ahmed E Othman, Sara Collorone, Ahmed T Toosy, Sven G Meuth, Frauke Zipp, Frederik Barkhof, Olga Ciccarelli, Sergiu Groppa
The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict five-year EDSS progression in patients
-
Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy Brain (IF 14.5) Pub Date : 2023-08-28 Mackenzie A Michell-Robinson, Kristin E N Watt, Vladimir Grouza, Julia Macintosh, Maxime Pinard, Marius Tuznik, Xiaoru Chen, Lama Darbelli, Chia-Lun Wu, Stefanie Perrier, Daryan Chitsaz, Nonthué A Uccelli, Hanwen Liu, Timothy C Cox, Christoph W Müller, Timothy E Kennedy, Benoit Coulombe, David A Rudko, Paul A Trainor, Geneviève Bernard
RNA polymerase III (Pol III)-related hypomyelinating leukodystrophy (POLR3-HLD), also known as 4H leukodystrophy, is a severe neurodegenerative disease characterized by the cardinal features of hypomyelination, hypodontia and hypogonadotropic hypogonadism. POLR3-HLD is caused by biallelic pathogenic variants in genes encoding Pol III subunits. While approximately half of all patients carry mutations
-
SUN1 facilitates CHMP7 nuclear influx and injury cascades in sporadic amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2023-08-28 Victoria Baskerville, Sampath Rapuri, Emma Mehlhop, Alyssa N Coyne
We have recently identified the aberrant nuclear accumulation of the ESCRT-III protein CHMP7 as an initiating event that leads to a significant injury to the nuclear pore complex (NPC) characterized by the reduction of specific nucleoporins (Nups) from the neuronal NPC in sporadic ALS (sALS) and C9orf72 ALS/FTD induced pluripotent stem cell (iPSC) derived neurons (iPSNs), a phenomenon also observed
-
Activated leukocyte cell adhesion molecule on human oligodendrocytes mediates CD4 T cell adhesion Brain (IF 14.5) Pub Date : 2023-08-28 Hélène Jamann, Haritha L Desu, Qiao-Ling Cui, Alexandre Halaweh, Olivier Tastet, Wendy Klement, Stephanie Zandee, Florian Pernin, Victoria H Mamane, Oumarou Ouédraogo, Audrey Daigneault, Hadjara Sidibé, Florence Millette, Evelyn Peelen, Tessa Dhaeze, Chloé Hoornaert, Rose-Marie Rébillard, Karine Thai, Camille Grasmuck, Christine Vande Velde, Alexandre Prat, Nathalie Arbour, Jo Anne Stratton, Jack Antel
Multiple sclerosis is a chronic neuroinflammatory disorder characterized by demyelination, oligodendrocyte damage/loss and neuroaxonal injury in the context of immune cell infiltration in the central nervous system. No neuroprotective therapy is available to promote the survival of oligodendrocytes and protect their myelin processes in immune-mediated demyelinating diseases. Pro-inflammatory CD4 Th17
-
Post-herpes simplex virus encephalitis autoimmunity: more the rule than the exception Brain (IF 14.5) Pub Date : 2023-08-28 Frank Leypoldt, Klaus-Peter Wandinger
This scientific commentary refers to ‘Herpes simplex encephalitis and neurologic alterations: clinical, immunological and genetic studies’ by Armangué et al. (https://doi.org/10.1093/brain/awad238).
-
Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome Brain (IF 14.5) Pub Date : 2023-08-24 Arthur S Walters, Yuqing Li, Brian B Koo, William G Ondo, Leonard B Weinstock, David Champion, Lawrence B Afrin, Elias G Karroum, Kanika Bagai, Karen Spruyt
Restless legs syndrome (RLS) is responsive to opioid, dopaminergic, and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin, and perhaps metenkephalin in the thalamus of RLS
-
Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome Brain (IF 14.5) Pub Date : 2023-08-24 Alexia Tiberi, Giulia Borgonovo, Giovanna Testa, Paola Pacifico, Ajesh Jacob, Mariachiara Di Caprio, Valentino Totaro, Mariantonietta Calvello, Antonino Cattaneo, Simona Capsoni
Rett syndrome is a rare genetic neurodevelopmental disease, affecting 1 in over 10,000 females born worldwide, caused by de novo mutations in the X-chromosome-located methyl-CpG-binding protein 2 (MeCP2) gene. Despite the great effort put forth by the scientific community, a therapy for this devastating disease is still needed. Here, we tested the therapeutic effects of a painless mutein of the Nerve
-
Toxic effects of mutant huntingtin in axons are mediated by its proline-rich domain Brain (IF 14.5) Pub Date : 2023-08-24 Scott T Brady, Nichole A Mesnard-Hoaglin, Mercedes Priego, Joanna Dziechciowska, Sarah Morris, Minsu Kang, Ming Ying Tsai, Jennifer L Purks, Alison Klein, Angelica Gaona, Alexandra Melloni, Theresa Connors, Bradley Hyman, Yuyu Song, Gerardo A Morfini
Huntington’s disease (HD) results from expansion of a polyglutamine tract (polyQ) in mutant huntingtin (mHTT) protein, but mechanisms underlying polyQ expansion-mediated toxic gain-of-mHTT function remain elusive. Here, deletion and antibody-based experiments revealed that a proline-rich domain (PRD) adjacent to the polyQ tract is necessary for mutant huntingtin (mHTT) to inhibit fast axonal transport
-
Astrogliosis marker 11C-SL2511.88 PET in traumatic brain injury with persistent symptoms Brain (IF 14.5) Pub Date : 2023-08-21 Yuko Koshimori, Michael D Cusimano, Erica L Vieira, Pablo M Rusjan, Stephen J Kish, Neil Vasdev, Sho Moriguchi, Isabelle Boileau, Thomas Chao, Zahra Nasser, M Ishrat Husain, Khunsa Faiz, Joeffre Braga, Jeffrey H Meyer
Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B total distribution volume ([11C]SL25.1188 VT)
-
Genetic topography and cortical cell loss in Huntington’s disease link development and neurodegeneration Brain (IF 14.5) Pub Date : 2023-08-17 Carlos Estevez-Fraga, Andre Altmann, Christopher S Parker, Rachael I Scahill, Beatrice Costa, Zhongbo Chen, Claudia Manzoni, Angeliki Zarkali, Alexandra Durr, Raymund A C Roos, Bernhard Landwehrmeyer, Blair R Leavitt, Geraint Rees, Sarah J Tabrizi, Peter McColgan
Cortical cell loss is a core feature of Huntington Disease (HD), beginning many years before clinical motor diagnosis, during the premanifest stage. However, it is unclear how genetic topography relates to cortical cell loss. Here, we explore the biological processes and cell types underlying this relationship and validate this using cell-specific post-mortem data. Eighty premanifest participants on
-
Observational studies of treatment effectiveness in neurology Brain (IF 14.5) Pub Date : 2023-08-16 Tomas Kalincik, Izanne Roos, Sifat Sharmin
The capacity and power of data from cohorts, registries and randomised trials to provide answers to contemporary clinical questions in neurology has increased considerably over the last two decades. Novel sophisticated statistical methods are enabling us to harness these data to guide treatment decisions, but their complexity is making appraisal of clinical evidence increasingly demanding. In this
-
Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2023-08-14 Shuangwu Liu, Xiaohan Sun, Qingguo Ren, Yujing Chen, Tingjun Dai, Yiru Yang, Gaolang Gong, Wei Li, Yuying Zhao, Xiangshui Meng, Pengfei Lin, Chuanzhu Yan
Recently, an astrocytic aquaporin 4-dependent drainage system, that is, the glymphatic system, has been identified in the live murine and human brain. Growing evidence suggests that glymphatic function is impaired in patients with several neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. As the third most common neurodegenerative disease, although animal studies have indicated
-
Investigating cortico-striatal beta oscillations in Parkinson's disease cognitive decline Brain (IF 14.5) Pub Date : 2023-08-14 Mansoureh Fahimi Hnazaee, Vladimir Litvak
This scientific commentary refers to ‘Corticostriatal beta oscillation changes associated with cognitive function in Parkinson’s disease’ by Paulo et al. (https://doi.org/10.1093/brain/awad206).
-
Injury patterns associated with cognitive motor dissociation Brain (IF 14.5) Pub Date : 2023-08-14 Eva Franzova, Qi Shen, Kevin Doyle, Justine M Chen, Jennifer Egbebike, Athina Vrosgou, Jerina C Carmona, Lauren Grobois, Gregory A Heinonen, Angela Velazquez, Ian Jerome Gonzales, Satoshi Egawa, Sachin Agarwal, David Roh, Soojin Park, E Sander Connolly, Jan Claassen
In unconscious appearing patients with acute brain injury, wilful brain activation to motor commands without behavioural signs of command following, known as cognitive motor dissociation (CMD), is associated with functional recovery. CMD can be detected by applying machine learning to EEG recorded during motor command presentation in behaviourally unresponsive patients. Identifying patients with CMD
-
Distinct tau folds initiate templated seeding and alter the post-translational modification profile Brain (IF 14.5) Pub Date : 2023-08-10 Airi Tarutani, Fuyuki Kametani, Marina Tahira, Yuko Saito, Mari Yoshida, Andrew C Robinson, David M A Mann, Shigeo Murayama, Taisuke Tomita, Masato Hasegawa
Pathological tau accumulates in the brain in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration, and forms amyloid-like filaments incorporating various post-translational modifications (PTMs). Cryo-electron microscopic (cryo-EM) studies have demonstrated that tau filaments extracted from tauopathy brains are characteristic of the disease
-
Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer’s disease mutations Brain (IF 14.5) Pub Date : 2023-08-08 Iason Keramidis, Brendan B McAllister, Julien Bourbonnais, Feng Wang, Dominique Isabel, Edris Rezaei, Romain Sansonetti, Phil Degagne, Justin P Hamel, Mojtaba Nazari, Samsoon Inayat, Jordan C Dudley, Annie Barbeau, Lionel Froux, Antoine G Godin, Majid H Mohajerani, Yves De Koninck
Disinhibition during early stages of Alzheimer’s disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer’s disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness
-
Homomeric interactions of the MPZ Ig domain and their relation to Charcot-Marie-Tooth disease Brain (IF 14.5) Pub Date : 2023-08-05 Christopher P Ptak, Tabitha A Peterson, Jesse B Hopkins, Christopher A Ahern, Michael E Shy, Robert C Piper
Mutations in MPZ (Myelin Protein Zero) can cause demyelinating early-onset Charcot-Marie-Tooth Type1B disease or later onset Type2I/J disease characterized by axonal degeneration, reflecting the diverse roles of MPZ in Schwann cells. MPZ holds apposing membranes of the myelin sheath together, with the adhesion role fulfilled by its extracellular Immunoglobulin-like domain (IgMPZ), which oligomerizes
-
Second messenger signaling bypasses CGRP receptor blockade to provoke migraine attacks in humans Brain (IF 14.5) Pub Date : 2023-08-04 Thien Phu Do, Christina Deligianni, Sarkhan Amirguliyev, Josefin Snellman, Cristina Lopez Lopez, Mohammad Al-Mahdi Al-Karagholi, Song Guo, Messoud Ashina
There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signaling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains
-
Cell-type specific and multiscale dynamics of human focal seizures in limbic structures Brain (IF 14.5) Pub Date : 2023-08-03 Alexander H Agopyan-Miu, Edward M Merricks, Elliot H Smith, Guy M McKhann, Sameer A Sheth, Neil A Feldstein, Andrew J Trevelyan, Catherine A Schevon
The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the seizure transition is complex, potentially leading to imprecise delineation of epileptogenic brain areas. In particular, the pattern of interneuronal firing at seizure onset remains under debate, with some studies demonstrating increased firing while others suggest reductions. Previous study of
-
How should we be using biomarkers in trials of disease modification in Parkinson’s disease? Brain (IF 14.5) Pub Date : 2023-08-03 Nirosen Vijiaratnam, Thomas Foltynie
The recent validation of the alpha synuclein seed amplification assay as a biomarker with high sensitivity and specificity for the diagnosis of Parkinson’s disease has formed the backbone for a proposed staging system for incorporation in Parkinson’s disease clinical studies and trials. The routine use of this biomarker should greatly aid in the accuracy of diagnosis during recruitment of Parkinson’s
-
The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer’s disease Brain (IF 14.5) Pub Date : 2023-08-02 Youjin Jung, Jessica S Damoiseaux
Over the last several years, there has been a surge in blood biomarker studies examining the value of plasma or serum neurofilament light (NfL) as a biomarker of neurodegeneration for Alzheimer’s disease (AD). However, there have been limited efforts to combine existing findings to assess the utility of blood NfL as a biomarker of neurodegeneration for AD. In addition, we still need better insight
-
The MLO-down on TDP-43 Brain (IF 14.5) Pub Date : 2023-08-02 Megan Dykstra, Sami J Barmada
This scientific commentary refers to ‘Transactive response DNA-binding protein 43 is enriched at the centrosome in human cells’ by Bodin et al. (https://doi.org/10.1093/brain/awad228).
-
Debates on the dorsomedial prefrontal/dorsal anterior cingulate cortex: insights for future research Brain (IF 14.5) Pub Date : 2023-08-02 Nicolas Clairis, Alizée Lopez-Persem
The dorsomedial prefrontal cortex/dorsal anterior cingulate cortex (dmPFC/dACC) is a brain area subject to many theories and debates over its function(s). Even its precise anatomical borders are subject to much controversy. In the past decades, the dmPFC/dACC has been associated with more than fifteen different cognitive processes, which sometimes appear quite unrelated (e.g., body perception, cognitive
-
Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice Brain (IF 14.5) Pub Date : 2023-08-01 Aydan Kahriman, James Bouley, Idil Tuncali, Elif O Dogan, Mariana Pereira, Thuyvan Luu, Daryl A Bosco, Samer Jaber, Owen M Peters, Robert H Brown, Nils Henninger
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury represents a risk factor for FTD and ALS, its role in exacerbating disease
-
Aggregation and beyond: alpha-synuclein-based biomarkers in synucleinopathies Brain (IF 14.5) Pub Date : 2023-08-01 Avika Chopra, Tiago Fleming Outeiro
Parkinson’s disease is clinically known for the loss of dopaminergic neurons in the substantia nigra pars compacta and accumulation of intraneuronal cytoplasmic inclusions rich in alpha-synuclein called ‘Lewy bodies’ and ‘Lewy neurites’. Together with dementia with Lewy bodies and multiple system atrophy, Parkinson’s disease is part of a group of disorders called synucleinopathies. Currently, diagnosis
-
Identifying sources of human interictal discharges with travelling wave and white matter propagation Brain (IF 14.5) Pub Date : 2023-08-01 C Price Withers, Joshua M Diamond, Braden Yang, Kathryn Snyder, Shervin Abdollahi, Joelle Sarlls, Julio I Chapeton, William H Theodore, Kareem A Zaghloul, Sara K Inati
Interictal epileptiform discharges have been shown to propagate from focal epileptogenic sources as traveling waves or through more rapid white matter conduction. We hypothesize that both modes of propagation are necessary to explain interictal discharge timing delays. We propose a method that for the first time incorporates both propagation modes to identify unique potential sources of interictal
-
Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders Brain (IF 14.5) Pub Date : 2023-07-30 Reza Maroofian, Rauan Kaiyrzhanov, Elisa Cali, Mina Zamani, Maha S Zaki, Matteo Ferla, Domenico Tortora, Saeid Sadeghian, Saadia Maryam Saadi, Uzma Abdullah, Ehsan Ghayoor Karimiani, Stephanie Efthymiou, Gözde Yeşil, Shahryar Alavi, Aisha M Al Shamsi, Homa Tajsharghi, Mohamed S Abdel-Hamid, Nebal Waill Saadi, Fuad Al Mutairi, Lama Alabdi, Christian Beetz, Zafar Ali, Mehran Beiraghi Toosi, Sabine Rudnik-Schöneborn
MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological
-
Neuromuscular disease genetics in underrepresented populations: increasing data diversity Brain (IF 14.5) Pub Date : 2023-07-30 Lindsay A Wilson, William L Macken, Luke D Perry, Christopher J Record, Katherine R Schon, Rodrigo S S Frezatti, Sharika Raga, Kireshnee Naidu, Özlem Yayıcı Köken, Ipek Polat, Musambo M Kapapa, Natalia Dominik, Stephanie Efthymiou, Heba Morsy, Melissa Nel, Mahmoud R Fassad, Fei Gao, Krutik Patel, Maryke Schoonen, Michelle Bisschoff, Armand Vorster, Hallgeir Jonvik, Ronel Human, Elsa Lubbe, Malebo Nonyane
Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers
-
The non-specific lethal complex regulates genes and pathways genetically linked to Parkinson’s disease Brain (IF 14.5) Pub Date : 2023-07-28 Amy R Hicks, Regina H Reynolds, Ben O’Callaghan, Sonia Garcia Ruiz, Ana Luisa Gil Martinez, Juan Botia, Helene Plun-Favreau, Mina Ryten
Genetic variants conferring risk for Parkinson’s disease have been highlighted through genome-wide association studies, yet exploration of their specific disease mechanisms is lacking. Two Parkinson’s disease candidate genes, KAT8 and KANSL1, identified through genome-wide studies and a PINK1-mitophagy screen, encode part of the histone acetylating non-specific lethal complex. This complex localises
-
Ablation of the carboxy-terminal end of MAMDC2 causes a distinct muscular dystrophy Brain (IF 14.5) Pub Date : 2023-07-28 Fabiola Mavillard, Emilia Servian-Morilla, Lein Dofash, Iñigo Rojas-Marcos, Chiara Folland, Gavin Monahan, Gerardo Gutierrez-Gutierrez, Eloy Rivas, Aurelio Hernández-Lain, Amador Valladares, Gloria Cantero, Jose M Morales, Nigel G Laing, Carmen Paradas, Gianina Ravenscroft, Macarena Cabrera-Serrano
The extracellular matrix (ECM) has an important role in the development and maintenance of skeletal muscle, and several muscle diseases are associated with the dysfunction of ECM elements. MAMDC2 is a putative ECM protein and its role in cell proliferation has been investigated in certain cancer types. However, its participation in skeletal muscle physiology has not been previously studied. We describe
-
Predictive coding and stochastic resonance as fundamental principles of auditory phantom perception Brain (IF 14.5) Pub Date : 2023-07-28 Achim Schilling, William Sedley, Richard Gerum, Claus Metzner, Konstantin Tziridis, Andreas Maier, Holger Schulze, Fan-Gang Zeng, Karl J Friston, Patrick Krauss
Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus – as the prime example of auditory phantom perception – we review recent work at the
-
Speech and language markers of neurodegeneration: a call for global equity Brain (IF 14.5) Pub Date : 2023-07-26 Adolfo M García, Jessica de Leon, Boon Lead Tee, Damián E Blasi, Maria Luisa Gorno-Tempini
In the field of neurodegeneration, speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other disorders. As a complement to classic tests, scalable and low-cost digital tools can capture relevant anomalies automatically, potentially supporting the quest for globally equitable markers of brain health. However, this promise remains unfulfilled due to limited