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Multiple sclerosis in Denmark (1950–2023): mean age, sex distribution, incidence and prevalence Brain (IF 10.6) Pub Date : 2024-07-20 Rolf P Holm, Malthe F Wandall-Holm, Melinda Magyari
With rising life expectancy and advancements in disease management, we expect the multiple sclerosis population is getting older. However, evidence supporting this hypothesis remains sparse. Our study aimed to determine whether the mean age of the Danish multiple sclerosis population has increased and to analyse the developments in sex distribution, incidence, and prevalence, all of which affect age
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Presynaptic hyperexcitability reversed by positive allosteric modulation of a GABABR epilepsy variant Brain (IF 10.6) Pub Date : 2024-07-19 Marielle Minere, Martin Mortensen, Valentina Dorovykh, Gary Warnes, Dean Nizetic, Trevor G Smart, Saad B Hannan
GABABRs are key membrane proteins that continually adapt the excitability of the nervous system. These G-protein coupled receptors are activated by the brain’s premier inhibitory neurotransmitter GABA. They are obligate heterodimers composed of GABA-binding GABABR1 and G-protein-coupling GABABR2 subunits. Recently, three variants (G693W, S695I, I705N) have been identified in the gene (GABBR2) encoding
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Shared patterns of glial transcriptional dysregulation link Huntington’s disease and schizophrenia Brain (IF 10.6) Pub Date : 2024-07-19 Nguyen P T Huynh, Mikhail Osipovitch, Rossana Foti, Janna Bates, Benjamin Mansky, Jose C Cano, Abdellatif Benraiss, Chuntao Zhao, Q Richard Lu, Steven A Goldman
Huntington’s disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction and hypomyelination. To assess whether a common mechanism might underlie the similar glial pathology of these otherwise disparate conditions, we used comparative correlation network approaches
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Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation Brain (IF 10.6) Pub Date : 2024-07-18 Tilman Schneider-Hohendorf, Christian Wünsch, Simon Falk, Catarina Raposo, Florian Rubelt, Hamid Mirebrahim, Hosseinali Asgharian, Ulrich Schlecht, Daniel Mattox, Wenyu Zhou, Eva Dawin, Marc Pawlitzki, Sarah Lauks, Sven Jarius, Brigitte Wildemann, Joachim Havla, Tania Kümpfel, Miriam-Carolina Schrot, Marius Ringelstein, Markus Kraemer, Carolin Schwake, Thomas Schmitter, Ilya Ayzenberg, Katinka Fischer
Epstein-Barr virus (EBV) infection has long been associated with the development of multiple sclerosis (MS). MS patients have elevated titers of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Regarding CD8+ T-cells, an elevated but ineffective response to EBV was suggested in MS patients, who present with a broader MHC-I-restricted EBV-specific T-cell receptor
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Combined clinical, structural, and cellular studies discriminate pathogenic and benign TRPV4 variants Brain (IF 10.6) Pub Date : 2024-07-18 Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karim, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A McCray
Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal
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Disentangling genetic risks for development and progression of Alzheimer’s disease Brain (IF 10.6) Pub Date : 2024-07-17 Niklas Mattsson-Carlgren
This scientific commentary refers to ‘Towards cascading genetic risk in Alzheimer’s disease’ by Altmann et al. (https://doi.org/10.1093/brain/awae176).
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The rich information hidden in misspoken discourse Brain (IF 10.6) Pub Date : 2024-07-16 Argye E Hillis
This scientific commentary refers to ‘Artificial intelligence classifies primary progressive aphasia from connected speech’ by Rezaii et al. (https://doi.org/10.1093/brain/awae196).
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Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer’s disease Brain (IF 10.6) Pub Date : 2024-07-16 Johanna Appleton, Quentin Finn, Paolo Zanotti-Fregonara, Meixiang Yu, Alireza Faridar, Mohammad O Nakawah, Carlos Zarate, Maria Carrillo, Bradford C Dickerson, Gil Rabinovici, Liana G Apostolova, Joseph C Masdeu, Belen Pascual
Brain inflammation, with an increased density of microglia and macrophages, is an important component of Alzheimer’s disease (AD) and a potential therapeutic target. However, it is incompletely characterized, particularly in patients whose disease begins before the age of 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged with translocator protein (TSPO) positron emission
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The graded multidimensional geometry of phenotypic variation and progression in neurodegenerative syndromes Brain (IF 10.6) Pub Date : 2024-07-15 Siddharth Ramanan, Danyal Akarca, Shalom K Henderson, Matthew A Rouse, Kieren Allinson, Karalyn Patterson, James B Rowe, Matthew A Lambon Ralph
Clinical variants of Alzheimer’s disease and frontotemporal lobar degeneration display a spectrum of cognitive-behavioural changes varying between individuals and over time. Understanding the landscape of these graded individual-/group-level longitudinal variations is critical for precise phenotyping; however, this remains challenging to model. Addressing this challenge, we leverage the National Alzheimer’s
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Systemic inflammatory markers in ageing, Alzheimer’s disease and other dementias Brain (IF 10.6) Pub Date : 2024-07-15 Huimin Cai, Tan Zhao, Yana Pang, Xiaofeng Fu, Ziye Ren, Shuiyue Quan, Longfei Jia
Systemic inflammation with alterations in inflammatory markers is involved in aging and Alzheimer’s disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during aging and Alzheimer’s disease, and specific markers contributing to Alzheimer’s disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical
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Customized antisense oligonucleotide-based therapy for neurofilament-associated Charcot-Marie-Tooth disease Brain (IF 10.6) Pub Date : 2024-07-15 Jessica Medina, Adriana Rebelo, Matt C Danzi, Elizabeth H Jacobs, Isaac R L Xu, Kathleen P Ahrens, Sitong Chen, Jacquelyn Raposo, Christopher Yanick, Stephan Zuchner, Mario A Saporta
DNA-based therapeutics have emerged as a revolutionary approach for addressing the treatment gap in rare inherited conditions by targeting the fundamental genetic causes of disease. Charcot-Marie-Tooth (CMT) disease, a group of inherited neuropathies, represents one of the most prevalent Mendelian disease groups in neurology and is characterized by diverse genetic etiology. Axonal forms of CMT, known
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Synaptic mitochondria glycation contributes to mitochondrial stress and cognitive dysfunction Brain (IF 10.6) Pub Date : 2024-07-13 Sourav Samanta, Firoz Akhter, Renhao Xue, Alexandre A Sosunov, Long Wu, Doris Chen, Ottavio Arancio, Shi Fang Yan, Shirley ShiDu Yan
Mitochondrial and synaptic dysfunction are pathological features of brain aging and cognitive decline. Synaptic mitochondria are vital for meeting the high energy demands of synaptic transmission. However, little is known about the link between age-related metabolic changes and the integrity of synaptic mitochondria. To this end, we investigate the mechanisms of advanced glycation endproducts (AGEs)-mediated
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Inflammation-induced mast cell-derived nerve growth factor: a key player in chronic vulvar pain? Brain (IF 10.6) Pub Date : 2024-07-13 Yaseen Awad-Igbaria, Doron Edelman, Elvira Ianshin, Saher Abu-Ata, Alon Shamir, Jacob Bornstein, Eilam Palzur
Provoked vulvodynia (PV) is characterized by localized chronic vulvar pain. It is associated with a history of recurrent inflammation, mast cell (MC) accumulation, and neuronal sprouting in the vulva. However, the mechanism of how vulvar-inflammation promotes neuronal sprouting and gene-expression adaptation in the spinal cord, leading to hypersensitivity and painful sensations, is unknown. Here, we
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Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissue Brain (IF 10.6) Pub Date : 2024-07-11 Valentina Marchica, Luca Biasetti, Jodi Barnard, Shujing Li, Nikolas Nikolaou, Matthew P Frosch, Diane E Lucente, Mark Eldaief, Andrew King, Manolis Fanto, Claire Troakes, Corinne Houart, Bradley N Smith
Annexin A11 mutations are a rare cause of amyotrophic lateral sclerosis (ALS), wherein replicated protein variants P36R, G38R, D40G and D40Y are located in a small-alpha helix within the long, disordered N-terminus. To elucidate disease mechanisms, we characterised the phenotypes induced by a genetic loss of function (LoF) and by misexpression of G38R and D40G in vivo. Loss of Annexin A11 results in
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Clinical and diagnostic implications of Alzheimer’s disease copathology in Lewy body disease Brain (IF 10.6) Pub Date : 2024-07-11 Lorenzo Barba, Samir Abu-Rumeileh, Henryk Barthel, Federico Massa, Matteo Foschi, Giovanni Bellomo, Lorenzo Gaetani, Dietmar R Thal, Lucilla Parnetti, Markus Otto
Concomitant Alzheimer’s disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with higher
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Side-effects are often a curse. Can they also be a blessing? Brain (IF 10.6) Pub Date : 2024-07-11 Katja Wiech, Helena Hartmann, Ulrike Bingel
This scientific commentary refers to ‘How side effects can improve treatment efficacy: a randomized trial’ by Schenk et al. (https://doi.org/10.1093/brain/awae132).
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Epileptic activity on foramen ovale electrodes is associated with sleep and tau pathology in Alzheimer’s disease Brain (IF 10.6) Pub Date : 2024-07-10 Astrid Devulder, Greet Vanderlinden, Leen Van Langenhoven, Dries Testelmans, Maarten Van Den Bossche, François-Laurent De Winter, Mathieu Vandenbulcke, Rik Vandenberghe, Tom Theys, Koen Van Laere, Wim Van Paesschen
Both sleep alterations and epileptiform activity are associated with the accumulation of amyloid-β and tau pathology and are currently investigated for potential therapeutic interventions in Alzheimer’s disease (AD). However, a bidirectional intertwining relation between sleep and neuronal hyperexcitability might modulate the effects of AD pathology on the corresponding associations. To investigate
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Piezo2 voltage-block regulates mechanical pain sensitivity Brain (IF 10.6) Pub Date : 2024-07-08 Oscar Sánchez-Carranza, Sampurna Chakrabarti, Johannes Kühnemund, Fred Schwaller, Valérie Bégay, Jonathan Alexis García-Contreras, Lin Wang, Gary R Lewin
PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurones in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available
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Gba1 E326K renders motor and non-motor symptoms with pathologic α-syn, tau and glial activation Brain (IF 10.6) Pub Date : 2024-07-08 Sin Ho Kweon, Hye Guk Ryu, Seung-Hwan Kwon, Hyeonwoo Park, Saebom Lee, Nam-Shik Kim, Shi-Xun Ma, Hee-Jung Jee, Sangjune Kim, Han Seok Ko
Mutations in the GBA1 gene are common genetic risk factors for Parkinson's disease (PD), disrupting enzymatic activity and causing lysosomal dysfunction, leading to elevated α-synuclein (α-syn) levels. While GBA1's role in synucleinopathy is well-established, recent research underscores neuroinflammation as a significant pathogenic mechanism in GBA1 deficiency. This study investigates neuroinflammation
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Neuronal A2A receptor exacerbates synapse loss and memory deficits in APP/PS1 mice Brain (IF 10.6) Pub Date : 2024-07-05 Victoria Gomez-Murcia, Agathe Launay, Kévin Carvalho, Anaëlle Burgard, Céline Meriaux, Raphaëlle Caillierez, Sabiha Eddarkaoui, Devrim Kilinc, Dolores Siedlecki-Wullich, Mélanie Besegher, Séverine Bégard, Bryan Thiroux, Matthieu Jung, Ouada Nebie, Maxence Wisztorski, Nicole Déglon, Claire Montmasson, Alexis-Pierre Bemelmans, Malika Hamdane, Thibaud Lebouvier, Didier Vieau, Isabelle Fournier, Luc Buee
Early pathological upregulation of adenosine A2A receptors (A2ARs), one of the caffeine targets, by neurons is thought to be involved in the development of synaptic and memory deficits in Alzheimer’s disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mice developing AD-like amyloidogenesis. Our findings
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A prefrontal-habenular circuitry regulates social fear behaviour Brain (IF 10.6) Pub Date : 2024-07-04 Yuanyuan Tian, Junqiang Zheng, Xiao Zhu, Xue Liu, Haoyang Li, Jun Wang, Qian Yang, Ling-Hui Zeng, Zhiguo Shi, Mengyuan Gong, Yuzheng Hu, Han Xu
The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting
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Great science does not communicate itself: but who should and how? Brain (IF 10.6) Pub Date : 2024-07-04 Cristina Kroon, Britta J Eickholt
Cristina Kroon and Britta Eickholt discuss current barriers to effective science communication and propose strategies to overcome them.
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Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson’s disease Brain (IF 10.6) Pub Date : 2024-07-02 Richard M Köhler, Thomas S Binns, Timon Merk, Guanyu Zhu, Zixiao Yin, Baotian Zhao, Meera Chikermane, Jojo Vanhoecke, Johannes L Busch, Jeroen G V Habets, Katharina Faust, Gerd-Helge Schneider, Alessia Cavallo, Stefan Haufe, Jianguo Zhang, Andrea A Kühn, John-Dylan Haynes, Wolf-Julian Neumann
The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up
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Ash1 l loss-of-function results in structural birth defects and altered cortical development Brain (IF 10.6) Pub Date : 2024-06-29 Kevin P Toolan, Brian T McGrath, Michelle L Brinkmeier, Sally A Camper, Stephanie L Bielas
The histone methyltransferase ASH1L plays a crucial role in regulating gene expression across various organ systems during development, yet its role in brain development remains largely unexplored. Over 130 individuals with autism harbour heterozygous loss-of-function ASH1L variants, and population studies confirm it as a high-risk autism gene. Previous studies on Ash1 l deficient mice have reported
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Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study Brain (IF 10.6) Pub Date : 2024-06-28 Elizaveta Mikhailenko, Kia Colangelo, Jarno Tuimala, Mia Kero, Sara Savola, Anna Raunio, Eloise H Kok, Maarit Tanskanen, Mira Mäkelä, Henri Puttonen, Mikko I Mäyränpää, Darshan Kumar, Karri Kaivola, Anders Paetau, Pentti J Tienari, Tuomo Polvikoski, Liisa Myllykangas
Population-based cohort studies are essential for understanding the pathological basis of dementia in older populations. Previous studies have shown that limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) increases with age, but there have been only a few studies, which have investigated this entity in a population-based setting. Here we studied the frequency of
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Putaminal dopamine modulates movement motivation in Parkinson’s disease Brain (IF 10.6) Pub Date : 2024-06-28 Magdalena Banwinkler, Verena Dzialas, Lionel Rigoux, Adrian L Asendorf, Hendrik Theis, Kathrin Giehl, Marc Tittgemeyer, Merle C Hoenig, Thilo van Eimeren
The relative inability to produce effortful movements is the most specific motor sign of Parkinson’s disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we
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Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes Brain (IF 10.6) Pub Date : 2024-06-28 Lorenzo Pasquini, Felipe L Pereira, Sahba Seddighi, Yi Zeng, Yongbin Wei, Ignacio Illán-Gala, Sarat C Vatsavayai, Adit Friedberg, Alex J Lee, Jesse A Brown, Salvatore Spina, Lea T Grinberg, Daniel W Sirkis, Luke W Bonham, Jennifer S Yokoyama, Adam L Boxer, Joel H Kramer, Howard J Rosen, Jack Humphrey, Aaron D Gitler, Bruce L Miller, Katherine S Pollard, Michael E Ward, William W Seeley
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of
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Nav1.2 channel mutations preventing fast inactivation lead to SCN2A encephalopathy Brain (IF 10.6) Pub Date : 2024-06-28 Géza Berecki, Elaine Tao, Katherine B Howell, Rohini K Coorg, Erik Andersen, Kris Kahlig, Markus Wolff, Ben Corry, Steven Petrou
SCN2A gene-related early-infantile developmental and epileptic encephalopathy (EI-DEE) is a rare and severe disorder that manifests in early infancy. SCN2A mutations affecting the fast inactivation gating mechanism can result in altered voltage dependence and incomplete inactivation of the encoded neuronal Nav1.2 channel and lead to abnormal neuronal excitability. In this study, we evaluated clinical
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Association of glial fibrillary acid protein, Alzheimer’s disease pathology and cognitive decline Brain (IF 10.6) Pub Date : 2024-06-26 Débora E Peretti, Cecilia Boccalini, Federica Ribaldi, Max Scheffler, Moira Marizzoni, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Giovanni B Frisoni, Valentina Garibotto
Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer’s disease. In this context, plasma levels of the glial fibrillary acidic protein (GFAP) have been suggested to have a robust association with Alzheimer’s disease pathophysiology. This study aims to assess the correlation between plasma GFAP and Alzheimer’s disease pathology
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Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy Brain (IF 10.6) Pub Date : 2024-06-25 Jintae Kim, Sang Min Park, Hyun Yong Koh, Ara Ko, Hoon-Chul Kang, Won Seok Chang, Dong Seok Kim, Jeong Ho Lee
Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioral seizures. The mosaic burdens
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Interplay between subthalamic nucleus and spinal cord controls parkinsonian nociceptive disorders Brain (IF 10.6) Pub Date : 2024-06-25 Keri-Ann Charles, Elba Molpeceres Sierra, Rabia Bouali-Benazzouz, Houyam Tibar, Khalid Oudaha, Frédéric Naudet, Alexia Duveau, Pascal Fossat, Abdelhamid Benazzouz
Background Pain is a non-motor symptom that impairs quality of life in Parkinson's patients. Pathological nociceptive hypersensitivity in patients could be due to changes in the processing of somatosensory information at the level of the basal ganglia, including the subthalamic nucleus (STN), but the underlying mechanisms are not yet defined. Here, we investigated the interaction between the STN and
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Distinct transcriptional alterations distinguish Lewy body disease from Alzheimer’s disease Brain (IF 10.6) Pub Date : 2024-06-25 Kimberly C Olney, Benjamin E Rabichow, Aleksandra M Wojtas, Michael DeTure, Pamela J McLean, Dennis W Dickson, Rui Chang, Owen A Ross, John D Fryer
Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by alpha-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast
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Brain repair mechanisms after cell therapy for stroke Brain (IF 10.6) Pub Date : 2024-06-25 Ruslan Rust, Lina R Nih, Luca Liberale, Hao Yin, Mohamad El Amki, Lin Kooi Ong, Berislav V Zlokovic
Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischemic stroke and then focus on how different stem and progenitor cell sources can promote
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A recurrent missense variant in ITPR3 causes demyelinating Charcot-Marie-Tooth with variable severity Brain (IF 10.6) Pub Date : 2024-06-24 Danique Beijer, Maike F Dohrn, Adriana Rebelo, Matt C Danzi, Bianca Rose Grosz, Melina Ellis, Kishore R Kumar, Steve Vucic, Horia Vais, Jillian S Weissenrieder, Olesia Lunko, Usha Paudel, Leah C Simpson, Jacquelyn Raposo, Mario Saporta, Yeisha Arcia, Isaac Xu, Shawna Feely, Christopher J Record, Julian Blake, Mary M Reilly, Steven Scherer, Marina Kennerson, Yi-Chung Lee, J Kevin Foskett, Michael Shy
Charcot-Marie-Tooth (CMT) disease is a neuromuscular disorder affecting the peripheral nervous system. The diagnostic yield in demyelinating CMT (CMT1) is typically ∼80-95%, of which at least 60% is due to the PMP22 gene duplication. The remainder of CMT1 is more genetically heterogeneous. We used whole exome and whole genome sequencing data included in the GENESIS database to investigate novel causal
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Artificial intelligence classifies primary progressive aphasia from connected speech Brain (IF 10.6) Pub Date : 2024-06-24 Neguine Rezaii, Daisy Hochberg, Megan Quimby, Bonnie Wong, Michael Brickhouse, Alexandra Touroutoglou, Bradford C Dickerson, Phillip Wolff
Neurodegenerative dementia syndromes, such as Primary Progressive Aphasias (PPA), have traditionally been diagnosed based in part on verbal and nonverbal cognitive profiles. Debate continues about whether PPA is best divided into three variants and also regarding the most distinctive linguistic features for classifying PPA variants. In this cross-sectional study, we first harnessed the capabilities
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Late-onset temporal lobe epilepsy: insights from brain atrophy and Alzheimer’s disease biomarkers Brain (IF 10.6) Pub Date : 2024-06-23 Alice Ballerini, Niccolò Biagioli, Chiara Carbone, Annalisa Chiari, Manuela Tondelli, Giulia Vinceti, Roberta Bedin, Marcella Malagoli, Maurilio Genovese, Simona Scolastico, Giada Giovannini, Matteo Pugnaghi, Niccolò Orlandi, Louis Lemieux, Stefano Meletti, Giovanna Zamboni, Anna Elisabetta Vaudano
Considering the growing age of the world population, the incidence of epilepsy in older adults is expected to increase significantly. It has been suggested that late-onset temporal lobe epilepsy (LO-TLE) may be neurodegenerative in origin and overlap with Alzheimer’s Disease (AD). Herein, we aimed to characterize the pattern of cortical atrophy and cerebrospinal fluid (CSF) biomarkers of AD (total
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Heterozygous variants in USP25 cause genetic generalized epilepsy Brain (IF 10.6) Pub Date : 2024-06-14 Cui-Xia Fan, Xiao-Rong Liu, Dao-Qi Mei, Bing-Mei Li, Wen-Bin Li, Huan-Cheng Xie, Jie Wang, Nan-Xiang Shen, Zi-Long Ye, Qiang-Long You, Ling-Ying Li, Xiao-Chong Qu, Li-Zhi Chen, Jin-Jie Liang, Ming-Rui Zhang, Na He, Jia Li, Jun-Ying Gao, Wei-Yi Deng, Wen-Zhe Liu, Wen-Ting Wang, Wei-Ping Liao, Qian Chen, Yi-Wu Shi
USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down’s syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy
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Explaining slow seizure propagation with white matter tractography Brain (IF 10.6) Pub Date : 2024-06-14 Abdullah Azeem, Chifaou Abdallah, Nicolás von Ellenrieder, Charbel El Kosseifi, Birgit Frauscher, Jean Gotman
Epileptic seizures recorded with stereoelectroencephalography (SEEG) can take a fraction of a second or several seconds to propagate from one region to another. What explains such propagation patterns? We combine tractography and SEEG to determine the relationship between seizure propagation and the white matter architecture and to describe seizure propagation mechanisms. Patient-specific spatiotemporal
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The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy Brain (IF 10.6) Pub Date : 2024-06-14 Derek J Doss, Jared S Shless, Sarah K Bick, Ghassan S Makhoul, Aarushi S Negi, Camden E Bibro, Rohan Rashingkar, Abhijeet Gummadavelli, Catie Chang, Martin J Gallagher, Robert P Naftel, Shilpa B Reddy, Shawniqua Williams-Roberson, Victoria L Morgan, Graham W Johnson, Dario J Englot
Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure
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Subthalamic control of impulsive actions: insights from deep brain stimulation in Parkinson’s disease Brain (IF 10.6) Pub Date : 2024-06-13 Damian M Herz, Michael J Frank, Huiling Tan, Sergiu Groppa
Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to
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The visual cortex in the blind but not the auditory cortex in the deaf becomes multiple-demand regions Brain (IF 10.6) Pub Date : 2024-06-12 Hasan Duymuş, Mohini Verma, Yasemin Güçlütürk, Mesut Öztürk, Ayşe B Varol, Şehmus Kurt, Tamer Gezici, Berhan F Akgür, İrem Giray, Elif E Öksüz, Ausaf A Farooqui
The fate of deprived sensory cortices – visual regions in the blind and auditory regions in the deaf – exemplifies the extent to which experience can change brain regions. These regions are frequently seen to activate during tasks involving other sensory modalities, leading many accounts to infer that these regions have started processing sensory information of other modalities. However, such observations
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Cholinergic deficiency in Parkinson’s disease patients with visual hallucinations Brain (IF 10.6) Pub Date : 2024-06-10 Emile d’Angremont, Sygrid van der Zee, Sofie Slingerland, Anne C Slomp, Erik F J de Vries, Teus van Laar, Iris E Sommer
Visual hallucinations (VH) can increase the burden of disease for both patients with Parkinson’s disease (PD) and their caregivers. Multiple neurotransmitters have been implicated in the neuropathology of VH, which provide targets for treatment and prevention. In this study, we assessed the association between cholinergic denervation and VH in PD in vivo, using PET imaging of the cholinergic system
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The readiness potential and the soul: what happens when you resect their seat in the brain? Brain (IF 10.6) Pub Date : 2024-05-31 Rickard L Sjöberg
Libet’s demonstration that activity in the supplementary motor area precedes conscious decision making is widely considered to have put the final nail in the coffin of dualism. Neurosurgeon Rickard Sjöberg argues that SMA resections show that Libet’s findings are in fact irrelevant to the neuroscientific discussion about free will.
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Investigation of network reorganization after epilepsy surgery is worth the effort Brain (IF 10.6) Pub Date : 2024-05-30 Lucas E Sainburg, Victoria L Morgan
This scientific commentary refers to ‘Connectome reorganization associated with temporal lobe pathology and its surgical resection’ by Larivière et al. (https://doi.org/10.1093/brain/awae141).
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Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport Brain (IF 10.6) Pub Date : 2024-05-29 Fatemeh Bahari, Volodymyr Dzhala, Trevor Balena, Kyle P Lillis, Kevin J Staley
Intraventricular hemorrhage (IVH) is a common complication of premature birth. Survivors are often left with cerebral palsy, intellectual disability, and/or hydrocephalus. Animal models suggest that brain tissue shrinkage with subsequent vascular stretch and tear is an important step in the pathophysiology, but the cause of this shrinkage is unknown. Clinical risk factors for IVH are biomarkers of
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Establishing connectivity through microdissections of midbrain stimulation-related neural circuits Brain (IF 10.6) Pub Date : 2024-05-29 Georgios P Skandalakis, Clemens Neudorfer, Caitlin A Payne, Evalina Bond, Armin D Tavakkoli, Jessica Barrios-Martinez, Anne C Trutti, Christos Koutsarnakis, Volker A Coenen, Spyridon Komaitis, Constantinos G Hadjipanayis, George Stranjalis, Fang-Cheng Yeh, Layla Banihashemi, Jennifer Hong, Andres M Lozano, Michael Kogan, Andreas Horn, Linton T Evans, Aristotelis Kalyvas
Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric
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Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function Brain (IF 10.6) Pub Date : 2024-05-28 Molly Braun, Mathew Sevao, Samantha A Keil, Elizabeth Gino, Marie X Wang, Janet Lee, Mariya A Haveliwala, Emily Klein, Sanjana Agarwal, Taylor Pedersen, C Harker Rhodes, Deidre Jansson, David Cook, Elaine Peskind, Daniel P Perl, Juan Piantino, Abigail G Schindler, Jeffrey J Iliff
Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer’s disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology
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Failure of C9orf72 sense repeat-targeting antisense oligonucleotides: lessons learned and the path forward Brain (IF 10.6) Pub Date : 2024-05-28 Alexander J Cammack, Rubika Balendra, Adrian M Isaacs
The recent failure of two independent clinical trials targeting C9orf72 sense repeat-containing RNAs with antisense oligonucleotides was a great disappointment for the field. Cammack et al. discuss the data from these trials, possible reasons for the failures, and the future of C9orf72 therapeutic targeting moving forward.
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Tiam1 is part of a novel mechanism for morphine tolerance and hyperalgesia Brain (IF 10.6) Pub Date : 2024-05-27 Elizaveta Mangutov, Amynah A Pradhan
This scientific commentary refers to ‘Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia’ by Yao et al. (https://doi.org/10.1093/brain/awae106).
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Biomechanical instability of the brain–CSF interface in hydrocephalus Brain (IF 10.6) Pub Date : 2024-05-27 Phan Q Duy, Neel H Mehta, Kristopher T Kahle
Hydrocephalus, characterized by progressive expansion of the cerebrospinal fluid (CSF)-filled ventricles (ventriculomegaly), is the most common reason for brain surgery. “Communicating” (i.e., non-obstructive) hydrocephalus is classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent CSF hypersecretion, impaired cilia-mediated CSF flow currents, or decreased
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Localization of stuttering based on causal brain lesions Brain (IF 10.6) Pub Date : 2024-05-27 Catherine Theys, Elina Jaakkola, Tracy R Melzer, Luc F De Nil, Frank H Guenther, Alexander L Cohen, Michael D Fox, Juho Joutsa
Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering. Here, we investigated the neuroanatomical substrate of stuttering using three independent datasets:
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Academic neurology in the UK: a plea to turn away from the precipice Brain (IF 10.6) Pub Date : 2024-05-21 Helen Devine, Edwin Jabbari, James Scott, Arpan R Mehta, Ruth Dobson, Simon Mead
Devine et al. argue that recent changes to clinical neurology training in the UK have the potential to exacerbate an existing crisis in academic neurology, and discuss what might be done to remedy the situation.
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Scn1a haploinsufficiency in the prefrontal cortex engages to cognitive impairment and depressive phenotype Brain (IF 10.6) Pub Date : 2024-05-21 Maurizio S Riga, Mercedes Pérez-Fernández, Lluis Miquel-Rio, Verónica Paz, Leticia Campa, Magdalena Martínez-Losa, Francisco J Esteban, Luis F Callado, Javier Meana, Francesc Artigas, Analía Bortolozzi, Manuel Álvarez-Dolado
Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.1 is a voltage-gated Na+ channel critical for normal GABAergic activity. Here, we studied the role of Nav1.1 in PFC function and its potential relationship with the aetiology of mental disorders
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Imbalanced mitochondrial dynamics contributes to the pathogenesis of X-linked adrenoleukodystrophy Brain (IF 10.6) Pub Date : 2024-05-20 Nathalie Launay, Jone Lopez-Erauskin, Patrizia Bianchi, Sanjib Guha, Janani Parameswaran, Andrea Coppa, Lorenzo Torreni, Agatha Schlüter, Stéphane Fourcade, Abraham J Paredes-Fuentes, Rafael Artuch, Carlos Casasnovas, Montserrat Ruiz, Aurora Pujol
The peroxisomal disease adrenoleukodystrophy (X-ALD) is caused by loss of the transporter of very-long-chain fatty acids (VLCFAs), ABCD1. An excess of VLCFAs disrupts essential homeostatic functions crucial for axonal maintenance, including redox metabolism, glycolysis and mitochondrial respiration. As mitochondrial function and morphology are intertwined, we set out to investigate the role of mitochondrial
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NMDA receptor autoantibodies primarily impair the extrasynaptic compartment Brain (IF 10.6) Pub Date : 2024-05-16 Zoe Jamet, Camille Mergaux, Morgane Meras, Delphine Bouchet, Frédéric Villega, Jakob Kreye, Harald Prüss, Laurent Groc
Autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR-Ab) are pathogenic immunoglobulins detected in patients suffering from NMDAR encephalitis. NMDAR-Ab alter the receptor membrane trafficking, synaptic transmission and neuronal network properties, leading to patients’ neurological and psychiatric symptoms. Patients often have very little neuronal damage but rapid and massive (
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De novo variants in ATXN7L3 lead to developmental delay, hypotonia and distinctive facial features Brain (IF 10.6) Pub Date : 2024-05-16 Tamar Harel, Camille Spicher, Elisabeth Scheer, Jillian G Buchan, Jennifer Cech, Chiara Folland, Tanja Frey, Alexander M Holtz, A Micheil Innes, Boris Keren, William L Macken, Carlo Marcelis, Catherine E Otten, Sarah A Paolucci, Florence Petit, Rolph Pfundt, Robert D S Pitceathly, Anita Rauch, Gianina Ravenscroft, Rani Sanchev, Katharina Steindl, Femke Tammer, Amanda Tyndall, Didier Devys, Stéphane
Deubiquitination is critical for the proper functioning of numerous biological pathways such as DNA repair, cell cycle progression, transcription, signal transduction, and autophagy. Accordingly, pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex,
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The vascular contribution of apolipoprotein E to Alzheimer's disease Brain (IF 10.6) Pub Date : 2024-05-15 Feng Chen, Jing Zhao, Fanxia Meng, Fangping He, Jie Ni, Yuan Fu
Alzheimer’s disease, the most prevalent form of dementia, imposes a substantial societal burden. The persistent inadequacy of disease-modifying drugs targeting amyloid plaques and neurofibrillary tangles suggests the contribution of alternative pathogenic mechanisms. A frequently overlooked aspect is cerebrovascular dysfunction, which may manifest early in the progression of Alzheimer’s disease pathology
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KATP channel mutation disrupts hippocampal network activity and nocturnal gamma shifts Brain (IF 10.6) Pub Date : 2024-05-14 Marie-Elisabeth Burkart, Josephine Kurzke, Robert Jacobi, Jorge Vera, Frances M Ashcroft, Jens Eilers, Kristina Lippmann
ATP-sensitive potassium (KATP) channels couple cell metabolism to cellular electrical activity. Humans affected by severe activating mutations in KATP channels suffer from developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). While the aetiology of diabetes in DEND syndrome is well understood, the pathophysiology of the neurological symptoms remains unclear. We hypothesised that impaired
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The implications of amyloid-β pathology: only time will tell Brain (IF 10.6) Pub Date : 2024-05-14 Emma M Coomans, Rik Ossenkoppele
This scientific commentary refers to ‘Characterizing brain tau and cognitive decline along the amyloid timeline in Alzheimer’s disease’ by Cody et al. (https://doi.org/10.1093/brain/awae116).
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Single-value brain activity scores reflect both severity and risk across the Alzheimer’s continuum Brain (IF 10.6) Pub Date : 2024-05-14 Joram Soch, Anni Richter, Jasmin M Kizilirmak, Hartmut Schütze, Gabriel Ziegler, Slawek Altenstein, Frederic Brosseron, Peter Dechent, Klaus Fliessbach, Silka Dawn Freiesleben, Wenzel Glanz, Daria Gref, Michael T Heneka, Stefan Hetzer, Enise I Incesoy, Ingo Kilimann, Okka Kimmich, Luca Kleineidam, Elizabeth Kuhn, Christoph Laske, Andrea Lohse, Falk Lüsebrink, Matthias H Munk, Oliver Peters, Lukas Preis
Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s