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Randomized Phase I Trial of the α-Synuclein Antibody Lu AF82422 Mov. Disord. (IF 8.6) Pub Date : 2024-03-17 Louise Buur, Jonas Wiedemann, Frank Larsen, Fayrouz Ben Alaya-Fourati, Pekka Kallunki, Dorte Kornerup Ditlevsen, Mette Høgh Sørensen, Didier Meulien
Immunotherapy targeting pathological α-synuclein (α-syn) species is a promising strategy for slowing disease progression in neurodegenerative synucleinopathies, including Parkinson's disease (PD).
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Neurological care for LGBT+ people Nat. Rev. Neurol. (IF 38.1) Pub Date : 2024-03-18 Salvatore Giovanni Volpe, Joya Ahmad, Roshni Abee Patel, Nicole Rosendale
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Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer’s disease Mol. Neurodegener. (IF 15.1) Pub Date : 2024-03-16 Hyo Jung Shin, In Soo Kim, Seung Gyu Choi, Kayoung Lee, Hyewon Park, Juhee Shin, Dayoung Kim, Jaewon Beom, Yoon Young Yi, Deepak Prasad Gupta, Gyun Jee Song, Won-Suk Chung, C. Justin Lee, Dong Woon Kim
Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia
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Clinical validation of the PrecivityAD2 blood test: A mass spectrometry‐based test with algorithm combining %p‐tau217 and Aβ42/40 ratio to identify presence of brain amyloid Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-16 Matthew R. Meyer, Kristopher M. Kirmess, Stephanie Eastwood, Traci L. Wente‐Roth, Faith Irvin, Mary S. Holubasch, Venky Venkatesh, Ilana Fogelman, Mark Monane, Lucy Hanna, Gil D. Rabinovici, Barry A. Siegel, Rachel A. Whitmer, Charles Apgar, Randall J. Bateman, David M. Holtzman, Michael Irizarry, David Verbel, Pallavi Sachdev, Satoshi Ito, John Contois, Kevin E. Yarasheski, Joel B. Braunstein, Philip
BACKGROUNDWith the availability of disease‐modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment.METHODSHigh‐throughput, mass spectrometry‐based assays were used to measure %p‐tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals
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Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-16 Marie‐Emmanuelle Riviere, Jessica B. Langbaum, R. Scott Turner, Juha O. Rinne, Yihan Sui, Pilar Cazorla, Javier Ricart, Kathleen Meneses, Angelika Caputo, Pierre N. Tariot, Eric M. Reiman, Ana Graf
INTRODUCTIONAlzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE‐1 inhibitor umibecestat in cognitively unimpaired 60‐ to 75‐year‐old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented.METHODSSixty‐five apolipoprotein E ε4
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Contribution of MRI for the Early Diagnosis of Parkinsonism in Patients with Diagnostic Uncertainty Mov. Disord. (IF 8.6) Pub Date : 2024-03-16 Lydia Chougar, Alice Faucher, Johann Faouzi, François‐Xavier Lejeune, Gonçalo Gama Lobo, Carna Jovanovic, Florence Cormier, Gwendoline Dupont, Marie Vidailhet, Jean‐Christophe Corvol, Olivier Colliot, Stéphane Lehéricy, David Grabli, Bertrand Degos
BackgroundInternational clinical criteria are the reference for the diagnosis of degenerative parkinsonism in clinical research, but they may lack sensitivity and specificity in the early stages.ObjectivesTo determine whether magnetic resonance imaging (MRI) analysis, through visual reading or machine‐learning approaches, improves diagnostic accuracy compared with clinical diagnosis at an early stage
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A New Definition of Psychosis Is Needed in Parkinson's Disease Mov. Disord. (IF 8.6) Pub Date : 2024-03-15 Joseph H. Friedman
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Short‐Term Cannabidiol with Δ‐9‐Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial Mov. Disord. (IF 8.6) Pub Date : 2024-03-15 Ying Liu, Jacquelyn Bainbridge, Stefan Sillau, Sarah Rajkovic, Michelle Adkins, Christopher H. Domen, John A. Thompson, Tristan Seawalt, Jost Klawitter, Cristina Sempio, Grace Chin, Lisa Forman, Michelle Fullard, Trevor Hawkins, Lauren Seeberger, Heike Newman, David Vu, Maureen Anne Leehey
BackgroundCannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks.ObjectiveThe aim is to study short‐term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ‐9‐tetrahydrocannabinol (THC) to provide preliminary data for a longer trial.MethodsPersons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating
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On‐Demand Cueing for Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial Mov. Disord. (IF 8.6) Pub Date : 2024-03-15 Demi Zoetewei, Talia Herman, Pieter Ginis, Luca Palmerini, Marina Brozgol, Pablo Cornejo Thumm, Alberto Ferrari, Eva Ceulemans, Eva Decaluwé, Jeffrey M. Hausdorff, Alice Nieuwboer
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Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 J. Matthijs Biesbroek, Mirthe Coenen, Charles DeCarli, Evan M. Fletcher, Pauline M. Maillard, , Frederik Barkhof, Josephine Barnes, Thomas Benke, Christopher P. L. H. Chen, Peter Dal-Bianco, Anna Dewenter, Marco Duering, Christian Enzinger, Michael Ewers, Lieza G. Exalto, Nicolai Franzmeier, Saima Hilal, Edith Hofer, Huiberdina L. Koek, Andrea B. Maier, Cheryl R. McCreary, Janne M. Papma, Ross W. Paterson
White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.
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Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease Brain (IF 14.5) Pub Date : 2024-03-14 Christopher J Record, Menelaos Pipis, Mariola Skorupinska, Julian Blake, Roy Poh, James M Polke, Kelly Eggleton, Tina Nanji, Stephan Zuchner, Andrea Cortese, Henry Houlden, Alexander M Rossor, Matilde Laura, Mary M Reilly
Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic diseases, but the diagnostic impact in CMT is yet to be fully reported. We present the diagnostic results from a single specialist inherited neuropathy centre, including
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Dementia, dementia's risk factors and premorbid brain structure are concentrated in disadvantaged areas: National register and birth‐cohort geographic analyses Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-14 Aaron Reuben, Leah S. Richmond‐Rakerd, Barry Milne, Devesh Shah, Amber Pearson, Sean Hogan, David Ireland, Ross Keenan, Annchen R. Knodt, Tracy Melzer, Richie Poulton, Sandhya Ramrakha, Ethan T. Whitman, Ahmad R. Hariri, Terrie E. Moffitt, Avshalom Caspi
INTRODUCTIONDementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level.METHODSWe tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20‐year observation. We then tested whether premorbid
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Correction to Association of Gut Microbiome with Diabetes Mellitus and Alzheimer's Disease in a Puerto Rican Adult Population: A Preliminary Report Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-14
Cecilia Michelle Soler-Llompart, Filipa Godoy-Vitorino, Ana Cecilia Sala-Morales, Michel Santiago-Berríos, Javier A. Ruiz-Adames, Gerianne Olivieri-Henry, Carlos Herrero-Rivera, Fabián J. Pérez-Luzunaris, Vanessa Sepulveda Association of Gut Microbiome with Diabetes Mellitus and Alzheimer's Disease in a Puerto Rican Adult Population: A Preliminary Report Alzheimer's Dement. 2023;19(Suppl. 24):e083053
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Adapting prescribing criteria for amyloid‐targeted antibodies for adults with Down syndrome Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-14 Hampus Hillerstrom, Richard Fisher, Matthew P. Janicki, Brian Chicoine, Bradley T. Christian, Anna Esbensen, Lucille Esralew, Juan Fortea, Sigan Hartley, Jason Hassenstab, Seth M. Keller, Sharon Krinsky‐McHale, Florence Lai, Johannes Levin, Mary McCarron, Eric McDade, Anne Sophie Rebillat, Herminia Diana Rosas, Wayne Silverman, Andre Strydom, Shahid H. Zaman, Henrik Zetterberg
Prior authorization criteria for Federal Drug Administration (FDA) approved immunotherapeutics, among the class of anti‐amyloid monoclonal antibodies (mAbs), established by state drug formulary committees, are tailored for adults with late‐onset Alzheimer's disease. This overlooks adults with Down syndrome (DS), who often experience dementia at a younger age and with different diagnostic assessment
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Cognitive Impairment Is Part of the Phenotype of Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) Mov. Disord. (IF 8.6) Pub Date : 2024-03-14 Kathy Dujardin, Céline Tard, Emily Diglé, Virginie Herlin, Eugénie Mutez, Jean‐Baptiste Davion, Anna Wissocq, Violette Delforge, Gregory Kuchcinski, Vincent Huin
BackgroundLittle is known about the impact of the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) on cognition.ObjectiveOur objective was to determine the frequency and severity of cognitive impairment in RFC1‐positive patients and describe the pattern of deficits.MethodsParticipants underwent a comprehensive neuropsychological assessment. Volume of the cerebellum and its lobules
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Longitudinal Free-Water Changes in Dementia with Lewy Bodies Mov. Disord. (IF 8.6) Pub Date : 2024-03-13 Shannon Y. Chiu, Robin Chen, Wei-en Wang, Melissa J. Armstrong, Bradley F. Boeve, Rodolfo Savica, Vijay Ramanan, Julie A. Fields, Neill Graff-Radford, Tanis J. Ferman, Kejal Kantarci, David E. Vaillancourt
Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results.
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Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia Acta Neuropathol. (IF 12.7) Pub Date : 2024-03-13 Christine Marques, Aaron Held, Katherine Dorfman, Joon Sung, Catherine Song, Amey S. Kavuturu, Corey Aguilar, Tommaso Russo, Derek H. Oakley, Mark W. Albers, Bradley T. Hyman, Leonard Petrucelli, Clotilde Lagier-Tourenne, Brian J. Wainger
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MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons Acta Neuropathol. (IF 12.7) Pub Date : 2024-03-12 Hong Xu, Qi Qiu, Peng Hu, Kevt’her Hoxha, Elliot Jang, Mia O’Reilly, Christopher Kim, Zhuohao He, Nicholas Marotta, Lakshmi Changolkar, Bin Zhang, Hao Wu, Gerard D. Schellenberg, Brian Kraemer, Kelvin C. Luk, Edward B. Lee, John Q. Trojanowski, Kurt R. Brunden, Virginia M.-Y. Lee
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Role of GBA variants in Lewy body disease neuropathology Acta Neuropathol. (IF 12.7) Pub Date : 2024-03-12
Abstract Rare and common GBA variants are risk factors for both Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological
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Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-12 Ryota Sakurai, Frederico Pieruccini-Faria, Benjamin Cornish, Julia Fraser, Malcolm A. Binns, Derek Beaton, Allison Ann Dilliott, Donna Kwan, Joel Ramirez, Brian Tan, Christopher J. M. Scott, Kelly M. Sunderland, Carmela Tartaglia, Elizabeth Finger, Lorne Zinman, Morris Freedman, Paula M. McLaughlin, Richard H. Swartz, Sean Symons, Anthony E. Lang, Robert Bartha, Sandra E. Black, Mario Masellis, Robert
Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases.
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Tests for consciousness in humans and beyond Trends Cogn. Sci. (IF 19.9) Pub Date : 2024-03-13 Tim Bayne, Anil K. Seth, Marcello Massimini, Joshua Shepherd, Axel Cleeremans, Stephen M. Fleming, Rafael Malach, Jason B. Mattingley, David K. Menon, Adrian M. Owen, Megan A.K. Peters, Adeel Razi, Liad Mudrik
Which systems/organisms are conscious? New tests for consciousness (‘C-tests’) are urgently needed. There is persisting uncertainty about when consciousness arises in human development, when it is lost due to neurological disorders and brain injury, and how it is distributed in nonhuman species. This need is amplified by recent and rapid developments in artificial intelligence (AI), neural organoids
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Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy Brain (IF 14.5) Pub Date : 2024-03-13 Caroline G Bergner, Marjolein Breur, M Clara Soto-Bernardini, Lisa Schäfer, Julia Lier, Diana Le Duc, Linnaeus Bundalian, Susanna Schubert, David Brenner, Friedmar R Kreuz, Björn Schulte, Quinten Waisfisz, Marianna Bugiani, Wolfgang Köhler, Heinrich Sticht, Rami Abou Jamra, Marjo S van der Knaap
Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. Recent years altered this perception, as a growing number of leukodystrophies was described to have an onset at adult ages. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16
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Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant Brain (IF 14.5) Pub Date : 2024-03-13 Beryll Blickhäuser, Sarah L Stenton, Christiane M Neuhofer, Elisa Floride, Victoria Nesbitt, Carl Fratter, Johannes Koch, Birgit Kauffmann, Claudia Catarino, Lea Dewi Schlieben, Robert Kopajtich, Valerio Carelli, Alfredo A Sadun, Robert McFarland, Fang Fang, Chiara La Morgia, Stéphanie Paquay, Marie Cécile Nassogne, Daniele Ghezzi, Costanza Lamperti, Saskia Wortmann, Jo Poulton, Thomas Klopstock, Holger
Leigh syndrome spectrum (LSS) is a primary mitochondrial disorder defined neuropathologically by a subacute necrotizing encephalomyelopathy and characterised by bilateral basal ganglia and/or brainstem lesions. LSS is associated with variants in several mitochondrial DNA (mtDNA) genes and more than 100 nuclear genes, most often related to mitochondrial complex I (CI) dysfunction. Rarely, LSS has been
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Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells Brain (IF 14.5) Pub Date : 2024-03-13 Hyuntae Kim, Nesrine Melliti, Eva Breithausen, Katrin Michel, Sara Ferrando Colomer, Ekaterina Poguzhelskaya, Paulina Nemcova, Laura Ewell, Sandra Blaess, Albert Becker, Julika Pitsch, Dirk Dietrich, Susanne Schoch
Full-length RIM1 and 2 are key components of the presynaptic active zone that ubiquitously control excitatory and inhibitory neurotransmitter release. Here, we report that the function of the small RIM isoform RIM4, consisting of a single C2 domain, is strikingly different from that of the long isoforms. RIM4 is dispensable for neurotransmitter release but plays a postsynaptic, cell-type specific role
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Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Marcia P. Jimenez, Emma L. Gause, Kendra D. Sims, Eleanor Hayes‐Larson, Emily P. Morris, Evan Fletcher, Jennifer Manly, Paola Gilsanz, Yenee Soh, Maria Corrada, Rachel A. Whitmer, Medellena Maria Glymour
INTRODUCTIONDepressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear.METHODSAsian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel
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APOE ε4 is associated with decreased synaptic density in cognitively impaired participants Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Kun He, Binyin Li, Jie Wang, Ying Wang, Zhiwen You, Xing Chen, Haijuan Chen, Junpeng Li, Qi Huang, Qihao Guo, Yiyun Henry Huang, Yihui Guan, Kewei Chen, Jun Zhao, Yulei Deng, Fang Xie
INTRODUCTIONWe aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants.METHODSOne hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F‐florbetapir and synaptic density PET with 18F‐SynVesT‐1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype
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Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Chiara Pappalettera, Claudia Carrarini, Francesca Miraglia, Fabrizio Vecchio, Paolo M. Rossini
INTRODUCTIONThis review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR
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Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-13 Robert Howard, Elizabeth Cort, Charlotte Rawlinson, Martin Wiegand, Anne Downey, Vanessa Lawrence, Sube Banerjee, Peter Bentham, Chris Fox, Rowan Harwood, Rachel Hunter, Gill Livingston, Esme Moniz‐Cook, Monica Panca, Malgorzata Raczek, Chineze Ivenso, Gregor Russell, Alan Thomas, Philip Wilkinson, Nicholas Freemantle, Rebecca Gould
INTRODUCTIONTrials of effectiveness of treatment options for depression in dementia are an important priority.METHODSRandomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease.RESULTSThree hundred thirty‐six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized
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Striatal and Extrastriatal Monoaminergic Disruption in Progressive Supranuclear Palsy Mov. Disord. (IF 8.6) Pub Date : 2024-03-13 Jing‐Hong Ma, Chong Dong, Hong‐Wen Qiao, Olivier Barret, Gilles D. Tamagnan, Wei Mao, Er‐He Xu, Chun Zhang, Jie Lu, Piu Chan, Shu‐Ying Liu
BackgroundAs a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18F‐9‐fluoropropyldihydrotetrabenazine (18F‐FP‐DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP).ObjectiveWe evaluated the striatal and extrastriatal monoaminergic
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Microglial Activation and Progression of Nigrostriatal Dysfunction in Isolated REM Sleep Behavior Disorder Mov. Disord. (IF 8.6) Pub Date : 2024-03-13 Kristian Stær, Alex Iranzo, Morten Gersel Stokholm, Victor S. Hvingelby, Erik Hvid Danielsen, Karen Østergaard, Mónica Serradell, Marit Otto, Kristina B. Svendsen, Alicia Garrido, Dolores Vilas, Joan Santamaria, Arne Møller, Carles Gaig, David J. Brooks, Per Borghammer, Eduardo Tolosa, Nicola Pavese
BackgroundUsing 11C‐(R)‐PK11195‐PET, we found increased microglia activation in isolated REM sleep behavior disorder (iRBD) patients. Their role remains to be clarified.ObjectivesThe objective is to assess relationships between activated microglia and progression of nigrostriatal dysfunction in iRBD.MethodsFifteen iRBD patients previously scanned with 11C‐(R)‐PK11195 and 18F‐DOPA‐PET underwent repeat
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Trans‐Spinal Theta Burst Magnetic Stimulation in Parkinson's Disease and Gait Disorders Mov. Disord. (IF 8.6) Pub Date : 2024-03-13 Janaína Reis Menezes, Glaucia Aline Nunes, Rafael Bernhart Carra, Juliana da Silva Simões, Davi Jorge Fontoura Solla, Jussan Rodrigues Oliveira, Manoel Jacobsen Teixeira, Marco Antônio Marcolin, Egberto Reis Barbosa, Clarice Tanaka, Daniel Ciampi de Andrade, Rubens Gisbert Cury
BackgroundGait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment.ObjectivesTo investigate the efficacy of intermittent θ burst trans‐spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders.MethodsThis was a randomized, parallel, double‐blind, controlled trial. Active or sham TsMS was applied at third
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APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward Aβ, through P2RY12 Mol. Neurodegener. (IF 15.1) Pub Date : 2024-03-11 Jordy Sepulveda, Jennifer Yejean Kim, Joseph Binder, Stefano Vicini, G. William Rebeck
Microglia are highly dynamic cells that play a critical role in tissue homeostasis through the surveillance of brain parenchyma and response to cues associated with damage. Aging and APOE4 genotype are the strongest risk factors for Alzheimer’s disease (AD), but how they affect microglial dynamics remains unclear. Using ex vivo confocal microscopy, we analyzed microglial dynamic behaviors in the entorhinal
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Alteration of LARGE1 abundance in patients and a mouse model of 5q-associated spinal muscular atrophy Acta Neuropathol. (IF 12.7) Pub Date : 2024-03-12
Abstract Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by recessive pathogenic variants affecting the survival of motor neuron (SMN1) gene (localized on 5q). In consequence, cells lack expression of the corresponding protein. This pathophysiological condition is clinically associated with motor neuron (MN) degeneration leading to severe muscular atrophy. Additionally, vulnerability
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Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson’s disease Acta Neuropathol. (IF 12.7) Pub Date : 2024-03-11
Abstract Parkinson’s disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research—l-DOPA remains the standard of care more than 50 years after its introduction. Here, we
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Genetic associations with dementia-related proteinopathy: Application of item response theory Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Yuriko Katsumata, David W. Fardo, Lincoln M. P. Shade, Xian Wu, Shama D. Karanth, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Kathryn Gauthreaux, Charles Mock, Walter A. Kukull, Erin L. Abner, Peter T. Nelson,
Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.
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Person‐specific differences in ubiquitin‐proteasome mediated proteostasis in human neurons Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-12 Yi‐Chen Hsieh, Zachary M. Augur, Mason Arbery, Nancy Ashour, Katharine Barrett, Richard V. Pearse, Earvin S. Tio, Duc M. Duong, Daniel Felsky, Philip L. De Jager, David A. Bennett, Nicholas T. Seyfried, Tracy L. Young‐Pearse
BACKGROUNDImpairment of the ubiquitin‐proteasome system (UPS) has been implicated in abnormal protein accumulation in Alzheimer's disease. It remains unclear if genetic variation affects the intrinsic properties of neurons that render some individuals more vulnerable to UPS impairment.METHODSInduced pluripotent stem cell (iPSC)‐derived neurons were generated from over 50 genetically variant and highly
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Effects of GPi DBS on Sensorimotor Integration in Dystonia: A Pilot ON/OFF Study Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Ana Paula Arantes, Nicole A. Zalasky, Ludymila Ribeiro Borges, Rachel E. Sondergaard, Davide Martino, Zelma H.T. Kiss
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Globus Pallidus Internus (GPi) Neuromodulation is Not Effective in Unverricht–Lundborg Disease to Control Myoclonia Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Gaëtan Poulen, Philippe Gélisse, Emilie Chan‐Seng, Pierre‐Olivier Moser, Pierre Genton, Arielle Crespel, Philippe Coubes
Unverricht–Lundborg disease (ULD), the most common and purest form of progressive myoclonus epilepsy (PME), follows an autosomal recessive transmission pattern, with onset typically between 8 and 13 years.1 Clinical outcomes can vary widely, ranging from minimal impairment to severe motor disability, including cases of bedridden patients.2 Bilateral globus pallidus internus (GPi) deep brain stimulation
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Abnormalities of the Descending Inhibitory Nociceptive Pathway in Functional Motor Disorders Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Giovanna Squintani, Christian Geroin, Alessia Pasquali, Eleonora Cavazzana, Alessia Segatti, Marianna Lippolis, Chiara Bonetto, Elena Antelmi, Michele Tinazzi
BackgroundPain is a common disabling non‐motor symptom affecting patients with functional motor disorders (FMD).ObjectiveWe aimed to explore ascending and descending nociceptive pathways with laser evoked potentials (LEPs) in FMD.MethodsWe studied a “bottom‐up and top‐down” noxious paradigm applying a conditioned pain modulation (CPM) protocol and recorded N2/P2 amplitude in 21 FMD and 20 controls
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Standing Balance Conditions and Digital Sway Measures for Clinical Trials of Friedreich's Ataxia Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Hannah L. Casey, Vrutangkumar V. Shah, Daniel Muzyka, James McNames, Mahmoud El‐Gohary, Kristen Sowalsky, Delaram Safarpour, Patricia Carlson‐Kuhta, Jeremy D. Schmahmann, Liana S. Rosenthal, Susan Perlman, Christian Rummey, Fay B. Horak, Christopher M. Gomez
BackgroundProgressive loss of standing balance is a feature of Friedreich's ataxia (FRDA).ObjectivesThis study aimed to identify standing balance conditions and digital postural sway measures that best discriminate between FRDA and healthy controls (HC). We assessed test–retest reliability and correlations between sway measures and clinical scores.MethodsTwenty‐eight subjects with FRDA and 20 HC completed
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The Motor Dysfunction Seen in Isolated REM Sleep Behavior Disorder Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Cristina Simonet, Laura Pérez‐Carbonell, Miquel A. Galmés‐Ordinas, Brook F.R. Huxford, Harneek Chohan, Aneet Gill, Guy Leschziner, Andrew J. Lees, Anette Schrag, Alastair J. Noyce
BackgroundIsolated Rapid Eye Movement (REM) sleep Behavior Disorder (iRBD) requires quantitative tools to detect incipient Parkinson's disease (PD).MethodsA motor battery was designed and compared with the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale part III (MDS‐UPDRS‐III) in people with iRBD and controls. This included two keyboard‐based tests (BRadykinesia Akinesia INcoordination
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ANO10‐Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Andona Milovanović, Ana Westenberger, Iva Stanković, Olivera Tamaš, Marija Branković, Ana Marjanović, Björn‐Hergen Laabs, Max Brand, Rajasumi Rajalingam, Connie Marras, Katja Lohmann, Vesna Branković, Ivana Novaković, Igor Petrović, Marina Svetel, Christine Klein, Vladimir S. Kostić, Natasa Dragašević‐Mišković
BackgroundBiallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX‐ANO10).MethodsFollowing the MDSGene protocol, we systematically investigated genotype–phenotype relationships in ATX‐ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients.ResultsMost patients (>80%) had loss‐of‐function (LOF) variants. The most common
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Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial Mov. Disord. (IF 8.6) Pub Date : 2024-03-12 Arianna Cappiello, Filomena Abate, Sarah Adamo, Maria Francesca Tepedino, Leandro Donisi, Carlo Ricciardi, Anna Rosa Avallone, Miriam Caterino, Sofia Cuoco, Maria Teresa Pellecchia, Marianna Amboni, Paolo Barone, Roberto Erro, Marina Picillo
BackgroundProgressive supranuclear palsy (PSP) is a rare 4R‐tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms.ObjectivesThis randomized, double‐blinded, sham‐controlled trial aimed at verifying the short‐, mid‐, and long‐term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP.MethodsTwenty‐five patients
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Updates on mouse models of Alzheimer’s disease Mol. Neurodegener. (IF 15.1) Pub Date : 2024-03-11 Michael Z. Zhong, Thomas Peng, Mariana Lemos Duarte, Minghui Wang, Dongming Cai
Alzheimer’s disease (AD) is the most common neurodegenerative disease in the United States (US). Animal models, specifically mouse models have been developed to better elucidate disease mechanisms and test therapeutic strategies for AD. A large portion of effort in the field was focused on developing transgenic (Tg) mouse models through over-expression of genetic mutations associated with familial
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The prevalence and topography of spinal cord demyelination in multiple sclerosis: a retrospective study Acta Neuropathol. (IF 12.7) Pub Date : 2024-03-09 Alex D. Waldman, Cecilia Catania, Marco Pisa, Mark Jenkinson, Michael J. Lenardo, Gabriele C. DeLuca
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Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial. JAMA Neurol. (IF 29.0) Pub Date : 2024-03-11 Hui-Sheng Chen, Yu Cui, Xin-Hong Wang, Yu-Tong Ma, Jing Han, Ying-Jie Duan, Jiang Lu, Li-Ying Shen, Yong Liang, Wei-Zhong Wang, Hui Wang, Yong Zhao, Jin-Tao Zhang, Yu-Lin Song, Xiao-Mei He, Run-Hui Li, Ding-Bo Tao, Jing Li, Shu-Man Huang, Ni Wang, Mei Hong, Chong Meng, Wei Zhang, Duo-Lao Wang, Thanh N Nguyen
Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking.
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Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis. JAMA Neurol. (IF 29.0) Pub Date : 2024-03-11 Anne H Cross, Jeffrey M Gelfand, Simon Thebault, Jeffrey L Bennett, H Christian von Büdingen, Briana Cameron, Robert Carruthers, Keith Edwards, Robert Fallis, Rachel Gerstein, Paul S Giacomini, Benjamin Greenberg, David A Hafler, Carolina Ionete, Ulrike W Kaunzner, Lay Kodama, Christopher Lock, Erin E Longbrake, Bruno Musch, Gabriel Pardo, Fredrik Piehl, Martin S Weber, Steven Yuen, Tjalf Ziemssen
Biomarkers distinguishing nonrelapsing progressive disease biology from relapsing biology in multiple sclerosis (MS) are lacking. Cerebrospinal fluid (CSF) is an accessible fluid that most closely reflects central nervous system biology.
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Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review. JAMA Neurol. (IF 29.0) Pub Date : 2024-03-11 Yu Kan Au, Mohammed F Kananeh, Rahul Rahangdale, Timothy Eoin Moore, Gregory A Panza, Nicolas Gaspard, Lawrence J Hirsch, Andres Fernandez, Syed Omar Shah
Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE.
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Microbleeds in Heterozygous HTRA1-Related Cerebral Small Vessel Disease. JAMA Neurol. (IF 29.0) Pub Date : 2024-03-11 Yu Guo, Qing Peng, Chen Ling
This case report describes the evaluation of a 44-year-old man with a history of headache, dizziness, and imbalance and imaging that showed lacunar infarctions and bilateral white matter hyperintensities.
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Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models Mov. Disord. (IF 8.6) Pub Date : 2024-03-11 Matthew J. Barrett, Ahmed Negida, Nitai Mukhopadhyay, Jin K. Kim, Huma Nawaz, Jefin Jose, Claudia Testa
BackgroundIntrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll‐HD.ObjectiveThe objective of this study was to investigate whether predictive models can accurately classify
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The Phenotypic and Genotypic Spectrum of CSF1R‐Related Disorder in China Mov. Disord. (IF 8.6) Pub Date : 2024-03-11 Jingying Wu, Xin Cheng, Duxin Ji, Huiwen Niu, Songquan Yao, Xukun Lv, Jianqiang Wang, Ziyi Li, Haoran Zheng, Yuwen Cao, Feixia Zhan, Mengyuan Zhang, Wotu Tian, Xiaojun Huang, Xinghua Luan, Li Cao
BackgroundColony‐stimulating factor 1 receptor (CSF1R)‐related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated.ObjectiveThe objective of the study is to clarify the core features and influence factors of CRD patients in China.MethodsClinical and genetic‐related data of CRD patients in China were collected. Mini‐Mental
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Towards the era of biological biomarkers for Parkinson disease Nat. Rev. Neurol. (IF 38.1) Pub Date : 2024-03-07 Nobutaka Hattori
Since its instigation in cancer research in the 1930s, the disease-staging concept has become a crucial tool in clinical research and medical practice. Two new papers have proposed biological staging and classification systems based on α-synuclein pathology for Parkinson disease and related conditions.
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Rural‐urban disparities in the diagnosis and treatment of hypertension and diabetes among aging Indians Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Pooja Rai, Pravin Sahadevan, Abhishek L. Mensegere, Thomas G. Issac, Graciela Muniz‐Terrera, Jonas S. Sundarakumar
INTRODUCTIONHypertension and diabetes are modifiable risk factors for dementia. We aimed to assess rural‐urban disparities in the diagnosis and treatment of these conditions among aging Indians.METHODSParticipants (n = 6316) were from two parallel, prospective aging cohorts in rural and urban India. Using self‐report and clinical/biochemical assessments, we subdivided participants with diabetes and
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BIN1K358R suppresses glial response to plaques in mouse model of Alzheimer's disease Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Laura Fernandez Garcia‐Agudo, Zechuan Shi, Ian F. Smith, Enikö A. Kramár, Katelynn Tran, Shimako Kawauchi, Shuling Wang, Sherilyn Collins, Amber Walker, Kai‐Xuan Shi, Jonathan Neumann, Heidi Yahan Liang, Celia Da Cunha, Giedre Milinkeviciute, Samuel Morabito, Emily Miyoshi, Narges Rezaie, Angela Gomez‐Arboledas, Adrian Mendoza Arvilla, Daryan Iman Ghaemi, Andrea J. Tenner, Frank M. LaFerla, Marcelo
INTRODUCTIONThe BIN1 coding variant rs138047593 (K358R) is linked to Late‐Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.METHODSTo elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock‐in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as
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Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-09 Gladys Maestre, Carl Hill, Percy Griffin, Stephen Hall, William Hu, Jason Flatt, Ganesh Babulal, Roland Thorpe, J. Neil Henderson, Dedra Buchwald, Spero Manson, Ethan Cicero, Andrea Gilmore‐Bykovskyi, Alyssa Gamaldo, Crystal Glover, Lisa Barnes, Amy Kind, Bryan James, Adina Zeki Al Hazzouri, Whitney Wharton, Paulo Caramelli, Sarah Szanton, Rachel Whitmer, Jada Benn Torres, Kacie Deters, Ozioma Okonkwo
Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well‐resourced, non‐Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's‐related risk factors in
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GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice Mol. Neurodegener. (IF 15.1) Pub Date : 2024-03-07 Ilaria Gregorio, Loris Russo, Enrica Torretta, Pietro Barbacini, Gabriella Contarini, Giada Pacinelli, Dario Bizzotto, Manuela Moriggi, Paola Braghetta, Francesco Papaleo, Cecilia Gelfi, Enrico Moro, Matilde Cescon
Mutations in the β-glucocerebrosidase (GBA1) gene do cause the lysosomal storage Gaucher disease (GD) and are among the most frequent genetic risk factors for Parkinson’s disease (PD). So far, studies on both neuronopathic GD and PD primarily focused on neuronal manifestations, besides the evaluation of microglial and astrocyte implication. White matter alterations were described in the central nervous
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Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients Alzheimers Dement. (IF 14.0) Pub Date : 2024-03-07 Marinus Fislage, Stefan Winzeck, Rebecca Woodrow, Florian Lammers-Lietz, Emmanuel A. Stamatakis, Marta M. Correia, Jacobus Preller, Insa Feinkohl, Jeroen Hendrikse, Tobias Pischon, Claudia D. Spies, Arjen J. C. Slooter, Georg Winterer, David K. Menon, Norman Zacharias
Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD).
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Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration Brain (IF 14.5) Pub Date : 2024-03-08 Fengfei Ding, Qian Sun, Carter Long, Rune Nguyen Rasmussen, Sisi Peng, Qiwu Xu, Ning Kang, Wei Song, Pia Weikop, Steven A Goldman, Maiken Nedergaard
Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal aging. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury since K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this
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The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders Brain (IF 14.5) Pub Date : 2024-03-08 Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias de Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar
Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural