Alexander Disease Research Update

Send us Fan MailAlbee Messing, Annette Bley, and Nadia Kokaly discuss the following recent publication: [01:58]       Description of the Hamburg Alexander Leukodystrophy Cohort-Insights into Practical Classification and the Care Situation. Journal of Clinical Medicine 14, 6918 (2025) [19:00]       Comment: Peer review – please come home. Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/ Podcasts are supported by Daniel's Fight (https://www.danielsfight.com).

Send us Fan MailAlbee Messing, Debra Levin, and Amy Waldman discuss the following recent publications: [01:27]       Language Skills in Patients With Alexander Disease. American Journal of Speech-Language Pathology 35:211-225 (2025) [17:06]       Characterization of Clinical Phenotype to Glial Fibrillary Acidic Protein Concentrations in Alexander Disease. Annals of Clinical and Translational Neurology (in press) [full text]Send your questions and feedback to:  [email protected] supported by Daniel's Fight. Help support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing and Amanda Nagy discuss the following recent publication: [01:42]       Genotype-phenotype correlations of GFAP variants in type I Alexander disease subtypesMolecular Genetics & Metabolism 147, 109689 (2026)Please send questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Tracy Hagemann, and Abby Olsen discuss the following recent publication: [01:45]       Growth Differentiation Factor 15 Elevation in the Central Nervous System Is Associated With Failure to Thrive in Alexander DiseaseAnnals of Clinical and Translational Neurology (in press) [full text]Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Mel Feany, and Natasha Snider discuss the following recent publication: Genotype-phenotype association for 14 GFAP variants in Alexander disease. Neurology: Genetics. 11, e200270 (2025) [full text] Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/    1.      Berman RF, Matson MR, Bachman AM, Lin N-H, Coyne S, Frelka A, et al. GFAP mutation and astrocyte dysfunction lead to a neurodegenerative profile with impaired synaptic plasticity and cognitive deficits in a rat model of Alexander disease. eNeuro:(in press) (2025) PMID: 40064497 Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications J Vis Exp, 18, 55655 (2017)STAT3 Drives GFAP Accumulation and Astrocyte Pathology in a Mouse Model of Alexander Disease Cells, 12, 978 (2023)A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells Stem Cell Reports, 18, 1701-1720 (2023) 

Send us Fan MailAlbee Messing, Tracy Hagemann, and Rob Berman discuss the following recent publication: [02:01]       GFAP mutation and astrocyte dysfunction lead to a neurodegenerative profile with impaired synaptic plasticity and cognitive deficits in a rat model of Alexander diseaseeNeuro (in press)  [full text]Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing, Charlie Wade, and Mel Feany discuss the following recent publication: [01:50]       Analysis of GFAP variants in UK Biobank suggests underdiagnosis or incomplete penetrance of adult-onset Alexander diseaseJournal of Neurology, Neurosurgery, and Psychiatry (in press) Please send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing and Natasha Snider discuss the following recent publications: [01:04]       Aberrant neurodevelopment in human iPS cell-derived models of Alexander disease                  Glia (2024) (in press)[16:46]       A novel GFAP frameshift variant identified in a family with optico-retinal dysplasia and vision impairmentHuman Molecular Genetics (2024) (in press)Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing’s presentation at the recent Alexander disease conference in Philadelphia, August 3, 2024. Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Amy Waldman, and Natasha Snider discuss the following recent publications: [02:07]       A retrospective observational cohort study of the anesthetic management and outcomes of pediatric patients with Alexander disease undergoing lumbar puncture or magnetic resonance imaging                  Paediatric Anesthessia (in press) [10:17]       Glial fibrillary acidic protein is pathologically modified in Alexander disease                  Journal of Biological Chemistry (in press) [full text]Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/   A retrospective observational cohort study of the anesthetic management and outcomes of pediatric patients with Alexander disease undergoing lumbar puncture or magnetic resonance imaging Paediatric Anaesthesia, (in press) (2024)  Glial fibrillary acidic protein is pathologically modified in Alexander disease Journal of Biological Chemistry, (in press) (2024)  

Send us Fan MailAlbee Messing, Jenny Pearson, Natasha Snider, and Amy Waldman discuss the following recent publication and the conference planned for this summer in Philadelphia: [02:02]       Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease         Neurological Sciences (2024)  [full text][04:16]       Discussion about Philadelphia Conference, August 2-4, 2024   Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing and Linghai Kong discuss the following recent publication: [01:52]       3D bioprinting of human neural tissues with functional connectivity. Cell Stem Cell 31:260-274.e7 (2024) [full text]Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/    Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications J Vis Exp, 18, 55655 (2017)STAT3 Drives GFAP Accumulation and Astrocyte Pathology in a Mouse Model of Alexander Disease Cells, 12, 978 (2023)A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells Stem Cell Reports, 18, 1701-1720 (2023) 

Send us Fan MailAlbee Messing, Rachel Battaglia, and Natasha Snider discuss the following publication: [00:59]       Intermediate filament dysregulation in astrocytes in the human disease model of KLHL16 mutation in giant axonal neuropathy (GAN)Molecular Biology of the Cell (in press)[full text - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10846626/]Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:            https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing, Nick Stowe, JP Yu, and Amy Waldman discuss the following recent publications: [4:30]          Stowe NA, Singh AP, Barnett BR, Yi SY, Frautschi PC, Messing A, et al. Quantitative diffusion imaging and genotype-by-sex interactions in a rat model of Alexander disease. Magnetic Resonance in Medicine (2023) in press[15:11]        Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease. Journal of Child Neurology (2023) in pressSend your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Rachel Battaglia, and Tracy Hagemann discuss the following recent publications: [01:45]       A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells                  Stem Cell Reports 18, 1701-1720 (2023)[includes new iPS cell line from an individual with Alexander disease] [full text][05:39]       Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational ModificationsJournal of Visualized Experiments 18, 55655 (2017)[includes data on acetylation of lysines in GFAP] [full text][10:26]       STAT3 Drives GFAP Accumulation and Astrocyte Pathology in a Mouse Model of Alexander Disease                  Cells 12, 978 (2023)[identification of one of the key mechanisms responsible for the increase in GFAP levels in Alexander disease] [full text][22:35]       Questions from email: does Alexander disease affect menstrual cycles?Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailWebinar on the strategy and preliminary results for “AAV-mediated Gene Silencing for the Treatment of Alexander Disease” presented by Drs. Guangping Gao, Jun Xie, and Dominic Gessler from the University of Massachusetts Medical School. This version is audio only - the full video version will be made available later at a site that is not yet determined.

Send us Fan MailAlbee Messing and Davide Tonduti discuss the following recent publication: [00:41]       Type I Alexander Disease: Update and Validation of the Clinical Evolution-Based ClassificationMolecular Genetics and Metabolism 138, 107540, 2023 [16:01]       Questions from email regarding mesenchymal stem cells for transplantation and the intranasal route for delivering therapeutics to the central nervous system. Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/  

Send us Fan MailAlbee Messing and Josh Bonkowsky discuss the following recent publication: [02:13]       Identification of a novel de novo pathogenic variant in GFAP in an Iranian family with Alexander disease by whole-exome sequencing.European Journal of Medical Research  27, 174 (2022) [full text][14:20]       Questions from email regarding the brainstem in Alexander disease.Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Emi Takahashi, Arastoo Vossough, and Amy Waldman discuss the following recent publication: [02:03]        Identification of association fibers using ex vivo diffusion tractography in Alexander disease brainsJournal of Neuroimaging (in press)Send your questions and feedback to:            [email protected]   

Send us Fan MailAlbee Messing, Rachel Battaglia, and Abby Olsen discuss the following recent publication: [01:00]        Alexander disease GFAP R239C mutant shows increased susceptibility to lipoxidation and elicits mitochondrial dysfunction and oxidative stress (Redox Biology, 55:102415, 2022)[14:23]       Questions from email regarding 1) dizziness and 2) risks of brain biopsies. Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing and Abby Olsen discuss the following recent publication: [03:04]       Adult-onset Alexander disease: new causal sequence variant in the GFAP gene. (Neurology: Genetics, in press) [14:15]       Autonomic nervous system – part 1 [26:09]       Questions from email regarding connecting spinal cord problems and symptoms. [31:17]       Autonomic nervous system – part 2Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/  

Send us Fan MailAlbee Messing and Natasha Snider discuss the following recent publication: [04:44]       Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments (Molecular Biology of the Cell, in press) [28:53]       Questions from email regarding heritability, penetrance, and skipping generations.Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/  

Send us Fan MailAlbee Messing, Mel Feany, Florian Eichler, and Ming der Perng discuss the following recent publications: [02:21]       Wang L et al. (2022) Anastasis drives senescence and non-cell autonomous neurodegeneration in the astrogliopathy Alexander disease. Journal of Neuroscience  (in press) [reports interesting new mechanisms of astrocyte dysfunction][18:42]       Kang YR et al. (2022). A novel in-frame GFAP p.E138_L148del mutation in Type II Alexander disease with atypical phenotypes.                   European Journal of Human Genetics  (in press)[case report describing unusual variant and symptoms, podcast includes commentary on head trauma and psychiatry]Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/  

Send us Fan MailAlbee Messing and Amy Waldman discuss the following recent publications: [01:08]       Mateos et al. (2022). Developmental delay and progressive seizures in 2-month-old child with diffuse MRI abnormalities. Brain Pathology  e13049[06:21]      Takeuchi et al. (2022) GFAP variant p. Tyr366Cys demonstrated widespread brain cavitation in neonatal Alexander disease. Radiology Case Reports  17, 771-774  [full text][13:48]       Mura et al. (2021). Alexander disease evolution over time: data from an Italian cohort of pediatric-onset patients. Molecular Genetics and Metabolism  134, 353-358[18:17]       Questions from email – how to manage constipation.Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/   

Send us Fan MailAlbee Messing and Michael Brenner discuss the following recent publications: [01:01]    Bachetti T et al.  (2021). Beneficial Effect of Phenytoin and Carbamazepine on GFAP Gene Expression and Mutant GFAP Folding in a Cellular Model of Alexander's Disease. Frontiers in Pharmacology 12, 723218  [full text][06:10]    Grossi A et al.  (2021). Parental Somatic Mosaicism Uncovers Inheritance of an Apparently De Novo GFAP Mutation. Frontiers in Genetics 12, 744068  [full text] [first convincing case of germline mosaicism in parent] [14:46]    Questions from email regarding the rat-ASO publication and variability in severity in humans.[17:52]    Murrray Brilliant joins to discuss how electronic health records are used in research and whether this will give us better estimates of national or world-wide numbers of people who have Alexander disease. Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Rachel Battaglia, and Peter Todd discuss the following recent publications: But first, revisiting the issue of “silent” mutations.[05:02]    Xu, S.Y. et al. (2021). Type II Alexander disease with fragile X mental retardation 1 gene mutation. Clinical Neurology and Neurosurgery 211, 107023 [18:25]    Hagemann, T.L. et al. (2021). Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment. Science Translational Medicine 13, eabg4711 (in press)[38:44]    Heaven, M.R. et al. (2021). Metabolic enzyme alterations and astrocyte dysfunction in a murine model of Alexander disease with severe reactive gliosis. Molecular and Cellular Proteomics 100180 (in press) [full text]          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing, Amy Waldman, and Nina Thomas discuss the following recent publications: [01:28]             Srivastava S, Waldman A, Naidu S (2020) Alexander disease. In: GeneReviews(®) (Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, eds). Seattle (WA): University of Washington, Seattle [review, focusing on clinical aspects] [full text][02:20]             Renaldo F, Chalard F, Valence S, Burglen L, Rodriguez D. (2021). Area postrema syndrome as the initial presentation of Alexander disease. Neurology  97, 548-549 [short case report][10:32]             Kirsch AC, McCall DM, Lange H, Renaud D, Brown T, Zaccariello MJ. (2021). Neuropsychological functioning in Alexander disease: a case series. Child Neurology Open  8, 2329048x211048614  [full text] [case #1 MRIs previously reported in Matarese 2008][21:36]             Questions from email regarding eligibility for blood/organ donation, optic neuropathies, and treatment for vomiting.Send your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/

Send us Fan MailAlbee Messing and Amy Waldman discuss the following recent publication: [00:40]             Amano E, Yoshida T, Mizuta I, Oyama J, Sakashita S, Ueyama S, Machida A, Yokota T. (2021). Activation of a Cryptic Splice Site of GFAP in a Patient With Adult-Onset Alexander Disease. Neurology Genetics. 7, e626 PMCID: PMC8488758Florian Eichler joins for a discussion about outcomes and clinical trials, prompted by:[13:09]             Questions from emailSend your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:           https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing, Berit Powers and Rachel Battaglia discuss the following recent publication: [4:11]     Nagata T et al. (2021). Cholesterol-functionalized DNA/RNA heteroduplexes cross the blood-brain barrier and knock down genes in the rodent CNS. Nat Biotechnol. (in press) PMID: 34385691[26:30]   Questions from emailSend your questions and feedback to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing and Amy Waldman discuss: [1:21] Cai T, Jing S, Li Y, Wu J. 2021. A Case Report of Adult-Onset Alexander Disease with a Tumor-Like Lesion in the Lateral Ventricle. Case Rep Neurol 13:355-360.  PMCID: PMC8255748[7:45} Yoshida T, Mizuta I, Yasuda R, Mizuno T. 2021. Clinical and radiological characteristics of older-adult-onset Alexander disease. Eur J Neurol (in press)[24:40] Questions from emailSend your questions to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:          https://alexander-disease.waisman.wisc.edu/donate/ 

Send us Fan MailAlbee Messing and Michael Brenner discuss:Hunt, CK, et al. Does genetic anticipation occur in familial Alexander disease? (2021). Neurogenetics (in press) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241638/https://medlineplus.gov/genetics/understanding/inheritance/anticipation/Send your questions to:  [email protected] support research on Alexander Disease at the University of Wisconsin-Madison's Waisman Center:                                                https://alexander-disease.waisman.wisc.edu/donate/