{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:07:47Z","timestamp":1790622467262,"version":"4.1.0"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013995","name":"Sanofi Genzyme","doi-asserted-by":"publisher","award":["GZ-2015-11321"],"award-info":[{"award-number":["GZ-2015-11321"]}],"id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD018482"],"award-info":[{"award-number":["S10OD018482"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Fabry disease is a rare X-linked deficiency of lysosomal alpha-galactosidase that causes glycolipid accumulation in tissues, including the brain. The most common neurologic sequelae of Fabry are cognitive decline and white matter lesions (WMLs) on brain magnetic resonance imaging (MRI). In the at-large population, however, WMLs are non-specific, highly prevalent, and most are clinically silent. Thus, we compared Fabry to typical brain aging to identify factors unique to Fabry-related cognitive decline. Twenty adult Fabry patients (75% female; median age 36.4 yrs, range: 19.8\u201363.2 yrs; 95% on enzyme replacement therapy) without a history of stroke or other neurologic diseases and 20 age\/sex-matched healthy controls were enrolled in a case-control study. All participants underwent a neurocognitive assessment and a 3.0 T MRI study of the brain that used structural MRI (e.g., fluid-attenuated inversion recovery, FLAIR), semi-quantitative MRI (e.g., normalized FLAIR signal intensity), and quantitative MRI (diffusion tensor imaging, bound-pool fraction imaging). During a blinded review of structural MRIs, a neuroradiologist\u2019s categorization of case-control status did not correspond to disease status (Fisher\u2019s test,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&gt;\u20090.99) but rather to age (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.004), indicating qualitative changes associated with Fabry were similar to normal age-related brain alterations. Using quantitative MRI, however, we detected evidence of microstructural damage in the white matter of younger Fabry adults (&lt;40 yrs). With age, WML severity increased and the corpus callosum atrophied in Fabry, phenomena absent in controls and consistent with progressive tissue damage. Neurocognitive assessments identified trends for lower verbal intelligence quotient and executive function in the younger Fabry participants, which became statistically significant in the older Fabry patients. Our data suggest that the early onset of microstructural damage in Fabry drives the insidious degeneration of white matter, leading to impaired cognition. Aging Fabry patients may benefit from serial cognitive assessments to identify unmet therapeutic needs.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0325403","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T18:24:01Z","timestamp":1763403841000},"page":"e0325403","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["The insidious degeneration of white matter and cognitive decline in Fabry disease"],"prefix":"10.1371","volume":"20","author":[{"given":"Jacob W.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hediyeh","family":"Baradaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jubel","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2055-9795","authenticated-orcid":true,"given":"Henrik","family":"Od\u00e8en","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Friel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon A.","family":"Zielinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7389-1487","authenticated-orcid":true,"given":"Hunter R.","family":"Underhill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"pone.0325403.ref001","volume-title":"Fabry Disease","author":"A Mehta","year":"1993"},{"issue":"2","key":"pone.0325403.ref002","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jmb.2004.01.035","article-title":"The molecular defect leading to Fabry disease: structure of human alpha-galactosidase","volume":"337","author":"SC Garman","year":"2004","journal-title":"J Mol Biol"},{"issue":"18","key":"pone.0325403.ref003","doi-asserted-by":"crossref","first-page":"10088","DOI":"10.3390\/ijms221810088","article-title":"Pathogenesis and Molecular Mechanisms of Anderson-Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies","volume":"22","author":"A Tuttolomondo","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0325403.ref004","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1161\/STROKEAHA.108.526293","article-title":"Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry","volume":"40","author":"K Sims","year":"2009","journal-title":"Stroke"},{"key":"pone.0325403.ref005","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1750-1172-8-47","article-title":"Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain","volume":"8","author":"SM Rombach","year":"2013","journal-title":"Orphanet J Rare Dis"},{"issue":"11","key":"pone.0325403.ref006","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1093\/brain\/awaa282","article-title":"White matter integrity correlates with cognition and disease severity in Fabry disease","volume":"143","author":"L Ulivi","year":"2020","journal-title":"Brain"},{"issue":"10","key":"pone.0325403.ref007","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1007\/s00415-023-11826-8","article-title":"Brain MRI correlations with disease burden and biomarkers in Fabry disease","volume":"270","author":"Y Zhao","year":"2023","journal-title":"J Neurol"},{"key":"pone.0325403.ref008","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jns.2018.10.009","article-title":"Brain MRI findings in children and adolescents with Fabry disease","volume":"395","author":"C Marchesoni","year":"2018","journal-title":"J Neurol Sci"},{"issue":"3","key":"pone.0325403.ref009","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ymgme.2018.08.014","article-title":"Development and clinical consequences of white matter lesions in Fabry disease: a systematic review","volume":"125","author":"S K\u00f6rver","year":"2018","journal-title":"Mol Genet Metab"},{"issue":"20","key":"pone.0325403.ref010","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1212\/WNL.0000000000002673","article-title":"Determinants of white matter hyperintensity burden in patients with Fabry disease","volume":"86","author":"NS Rost","year":"2016","journal-title":"Neurology"},{"issue":"2","key":"pone.0325403.ref011","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/j.1468-1331.2010.03155.x","article-title":"Neuropsychiatric symptoms and brain structural alterations in Fabry disease","volume":"18","author":"I Schermuly","year":"2011","journal-title":"Eur J Neurol"},{"key":"pone.0325403.ref012","first-page":"73","article-title":"Cognitive Impairments and Subjective Cognitive Complaints in Fabry Disease: A Nationwide Study and Review of the Literature","volume":"41","author":"J Loeb","year":"2018","journal-title":"JIMD Rep"},{"issue":"4","key":"pone.0325403.ref013","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s10545-010-9133-3","article-title":"Psychiatric and cognitive profile in Anderson-Fabry patients: a preliminary study","volume":"33","author":"P Segal","year":"2010","journal-title":"J Inherit Metab Dis"},{"issue":"7","key":"pone.0325403.ref014","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1093\/arclin\/acu047","article-title":"Cognitive and psychological functioning in Fabry disease","volume":"29","author":"L Sigmundsdottir","year":"2014","journal-title":"Arch Clin Neuropsychol"},{"issue":"4","key":"pone.0325403.ref015","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/jimd.12472","article-title":"Cognitive dysfunction and white matter hyperintensities in Fabry disease","volume":"45","author":"P Murphy","year":"2022","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"pone.0325403.ref016","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJM200107053450102","article-title":"Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry\u2019s disease","volume":"345","author":"CM Eng","year":"2001","journal-title":"N Engl J Med"},{"issue":"6","key":"pone.0325403.ref017","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1159\/000369293","article-title":"Enzyme replacement therapy stabilized white matter lesion progression in Fabry disease","volume":"38","author":"A Fellgiebel","year":"2014","journal-title":"Cerebrovasc Dis"},{"key":"pone.0325403.ref018","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ymgme.2016.06.007","article-title":"Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry","volume":"119","author":"RJ Hopkin","year":"2016","journal-title":"Mol Genet Metab"},{"issue":"5","key":"pone.0325403.ref019","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1002\/jimd.12271","article-title":"Cognitive functioning and depressive symptoms in Fabry disease: A follow-up study","volume":"43","author":"S K\u00f6rver","year":"2020","journal-title":"J Inherit Metab Dis"},{"key":"pone.0325403.ref020","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/brain\/awf077","article-title":"Hypertension and cerebral white matter lesions in a prospective cohort study","volume":"125","author":"F-E de Leeuw","year":"2002","journal-title":"Brain"},{"key":"pone.0325403.ref021","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.trci.2019.02.001","article-title":"White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities","volume":"5","author":"J Alber","year":"2019","journal-title":"Alzheimers Dement (N Y)"},{"issue":"10","key":"pone.0325403.ref022","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3174\/ajnr.A8001","article-title":"Progressive Changes in Cerebral Apparent Diffusion Values in Fabry Disease: A 5-Year Follow-up MRI Study","volume":"44","author":"KPA Baas","year":"2023","journal-title":"AJNR Am J Neuroradiol"},{"issue":"5","key":"pone.0325403.ref023","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00234-012-1131-8","article-title":"Diffusion tensor imaging and brain volumetry in Fabry disease patients","volume":"55","author":"T Paavilainen","year":"2013","journal-title":"Neuroradiology"},{"issue":"6","key":"pone.0325403.ref024","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/jmri.24952","article-title":"Detecting the effects of Fabry disease in the adult human brain with diffusion tensor imaging and fast bound-pool fraction imaging","volume":"42","author":"HR Underhill","year":"2015","journal-title":"J Magn Reson Imaging"},{"issue":"4","key":"pone.0325403.ref025","doi-asserted-by":"crossref","DOI":"10.1093\/braincomms\/fcac187","article-title":"Structural disconnection and functional reorganization in Fabry disease: a multimodal MRI study","volume":"4","author":"I Gabusi","year":"2022","journal-title":"Brain Commun"},{"issue":"2","key":"pone.0325403.ref026","first-page":"226","article-title":"Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study","volume":"28","author":"SM Grieve","year":"2007","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0325403.ref027","first-page":"9","article-title":"Age-Related Differences in White Matter Integrity in Healthy Human Brain: Evidence from Structural MRI and Diffusion Tensor Imaging","volume":"9","author":"R Rathee","year":"2016","journal-title":"Magn Reson Insights"},{"issue":"3","key":"pone.0325403.ref028","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/j.neuroimage.2010.10.065","article-title":"Fast bound pool fraction imaging of the in vivo rat brain: association with myelin content and validation in the C6 glioma model","volume":"54","author":"HR Underhill","year":"2011","journal-title":"Neuroimage"},{"issue":"1","key":"pone.0325403.ref029","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1148\/radiol.14140528","article-title":"Fast whole-brain three-dimensional macromolecular proton fraction mapping in multiple sclerosis","volume":"274","author":"VL Yarnykh","year":"2015","journal-title":"Radiology"},{"issue":"1","key":"pone.0325403.ref030","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41398-021-01475-8","article-title":"Global hypomyelination of the brain white and gray matter in schizophrenia: quantitative imaging using macromolecular proton fraction","volume":"11","author":"LP Smirnova","year":"2021","journal-title":"Transl Psychiatry"},{"issue":"997","key":"pone.0325403.ref031","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1259\/bjr\/21946513","article-title":"The corpus callosum: white matter or terra incognita","volume":"84","author":"A Fitsiori","year":"2011","journal-title":"Br J Radiol"},{"issue":"6","key":"pone.0325403.ref032","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00234-017-1829-8","article-title":"Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis","volume":"59","author":"S Cocozza","year":"2017","journal-title":"Neuroradiology"},{"issue":"11","key":"pone.0325403.ref033","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.1121","article-title":"Absence of infratentorial lesions in Fabry disease contributes to differential diagnosis with multiple sclerosis","volume":"8","author":"L Ugga","year":"2018","journal-title":"Brain Behav"},{"issue":"6","key":"pone.0325403.ref034","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1002\/mrm.10171","article-title":"Generalized autocalibrating partially parallel acquisitions (GRAPPA)","volume":"47","author":"MA Griswold","year":"2002","journal-title":"Magn Reson Med"},{"issue":"4","key":"pone.0325403.ref035","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/mrm.1910370426","article-title":"An extended two-point Dixon algorithm for calculating separate water, fat, and B0 images","volume":"37","author":"TE Skinner","year":"1997","journal-title":"Magn Reson Med"},{"issue":"1","key":"pone.0325403.ref036","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/mrm.21120","article-title":"Actual flip-angle imaging in the pulsed steady state: a method for rapid three-dimensional mapping of the transmitted radiofrequency field","volume":"57","author":"VL Yarnykh","year":"2007","journal-title":"Magn Reson Med"},{"issue":"1","key":"pone.0325403.ref037","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuroimage.2004.04.029","article-title":"Cross-relaxation imaging reveals detailed anatomy of white matter fiber tracts in the human brain","volume":"23","author":"VL Yarnykh","year":"2004","journal-title":"Neuroimage"},{"issue":"2","key":"pone.0325403.ref038","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2214\/ajr.149.2.351","article-title":"MR signal abnormalities at 1.5 T in Alzheimer\u2019s dementia and normal aging","volume":"149","author":"F Fazekas","year":"1987","journal-title":"AJR Am J Roentgenol"},{"key":"pone.0325403.ref039","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuroimage.2018.05.027","article-title":"Population-averaged atlas of the macroscale human structural connectome and its network topology","volume":"178","author":"F-C Yeh","year":"2018","journal-title":"Neuroimage"},{"issue":"2","key":"pone.0325403.ref040","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/mrm.26143","article-title":"Mapping immune cell infiltration using restricted diffusion MRI","volume":"77","author":"F-C Yeh","year":"2017","journal-title":"Magn Reson Med"},{"issue":"9","key":"pone.0325403.ref041","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1109\/TMI.2010.2045126","article-title":"Generalized q-sampling imaging","volume":"29","author":"F-C Yeh","year":"2010","journal-title":"IEEE Trans Med Imaging"},{"issue":"3","key":"pone.0325403.ref042","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1037\/a0023810","article-title":"Effects of aging and IQ on item and associative memory","volume":"140","author":"R Ratcliff","year":"2011","journal-title":"J Exp Psychol Gen"},{"issue":"2","key":"pone.0325403.ref043","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/gps.2087","article-title":"Aging of cerebral white matter: a review of MRI findings","volume":"24","author":"FM Gunning-Dixon","year":"2009","journal-title":"Int J Geriatr Psychiatry"},{"issue":"6","key":"pone.0325403.ref044","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.cmet.2018.05.011","article-title":"Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States","volume":"27","author":"MP Mattson","year":"2018","journal-title":"Cell Metab"},{"issue":"4","key":"pone.0325403.ref045","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1016\/j.neuroimage.2009.05.075","article-title":"Direct quantitative comparison between cross-relaxation imaging and diffusion tensor imaging of the human brain at 3.0 T","volume":"47","author":"HR Underhill","year":"2009","journal-title":"Neuroimage"},{"key":"pone.0325403.ref046","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropsychologia.2014.06.003","article-title":"Verbal learning and memory in agenesis of the corpus callosum","volume":"60","author":"RL Erickson","year":"2014","journal-title":"Neuropsychologia"},{"issue":"4","key":"pone.0325403.ref047","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrn2107","article-title":"Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity","volume":"8","author":"LK Paul","year":"2007","journal-title":"Nat Rev Neurosci"},{"issue":"10","key":"pone.0325403.ref048","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0258469","article-title":"Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children","volume":"16","author":"AT Marshall","year":"2021","journal-title":"PLoS One"},{"issue":"4","key":"pone.0325403.ref049","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/ane.12006","article-title":"Callosal atrophy in multiple sclerosis is related to cognitive speed","volume":"127","author":"G Bergendal","year":"2013","journal-title":"Acta Neurol Scand"},{"issue":"2","key":"pone.0325403.ref050","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1001\/archneur.59.2.243","article-title":"Progression of corpus callosum atrophy in Alzheimer disease","volume":"59","author":"SJ Teipel","year":"2002","journal-title":"Arch Neurol"},{"issue":"3","key":"pone.0325403.ref051","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1177\/1352458513496880","article-title":"The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients","volume":"20","author":"\u00d6 Yaldizli","year":"2014","journal-title":"Mult Scler"},{"issue":"1","key":"pone.0325403.ref052","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3233\/JAD-2010-1370","article-title":"In vivo structural neuroanatomy of corpus callosum in Alzheimer\u2019s disease and mild cognitive impairment using different MRI techniques: a review","volume":"20","author":"M Di Paola","year":"2010","journal-title":"J Alzheimers Dis"},{"issue":"13","key":"pone.0325403.ref053","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1212\/WNL.0000000000003764","article-title":"Corpus callosal atrophy and associations with cognitive impairment in Parkinson disease","volume":"88","author":"JG Goldman","year":"2017","journal-title":"Neurology"},{"issue":"2","key":"pone.0325403.ref054","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3390\/jcm8020167","article-title":"White Matter Changes in Patients with Alzheimer\u2019s Disease and Associated Factors","volume":"8","author":"Y-H Kao","year":"2019","journal-title":"J Clin Med"},{"issue":"4","key":"pone.0325403.ref055","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrneurol.2011.21","article-title":"White matter lesions in Parkinson disease","volume":"7","author":"NI Bohnen","year":"2011","journal-title":"Nat Rev Neurol"},{"key":"pone.0325403.ref056","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1001\/jamanetworkopen.2024.41505","article-title":"Acceleration of Brain Atrophy and Progression From Normal Cognition to Mild Cognitive Impairment","volume":"7","author":"Y Uchida","year":"2024","journal-title":"JAMA Netw Open"},{"issue":"33","key":"pone.0325403.ref057","doi-asserted-by":"crossref","first-page":"13642","DOI":"10.1073\/pnas.1303346110","article-title":"Energetic cost of brain functional connectivity","volume":"110","author":"D Tomasi","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0325403.ref058","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF00697017","article-title":"Neuropathological and biochemical studies in Fabry\u2019s disease","volume":"30","author":"T Tabira","year":"1974","journal-title":"Acta Neuropathol"},{"issue":"4","key":"pone.0325403.ref059","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1001\/archneur.1971.00490040077009","article-title":"the central nervous system in Fabry\u2019s disease. A clinical, pathological, and biochemical investigation","volume":"25","author":"HO Lou","year":"1971","journal-title":"Arch Neurol"},{"issue":"5","key":"pone.0325403.ref060","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1440-1789.2008.00883.x","article-title":"An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia","volume":"28","author":"R Okeda","year":"2008","journal-title":"Neuropathology"},{"key":"pone.0325403.ref061","article-title":"Fabry disease in females: clinical characteristics and effects of enzyme replacement therapy.","volume-title":"Fabry Disease: Perspectives from 5 Years of FOS","author":"PB Deegan","year":"2006"},{"issue":"6","key":"pone.0325403.ref062","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s10545-014-9717-4","article-title":"Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study","volume":"37","author":"LJ Anderson","year":"2014","journal-title":"J Inherit Metab Dis"},{"issue":"7","key":"pone.0325403.ref063","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/jmedgenet-2015-103486","article-title":"Time to treatment benefit for adult patients with Fabry disease receiving agalsidase \u03b2: data from the Fabry Registry","volume":"53","author":"A Ortiz","year":"2016","journal-title":"J Med Genet"},{"issue":"4","key":"pone.0325403.ref064","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ymgme.2014.01.014","article-title":"Outcomes of patients treated through the Canadian Fabry disease initiative","volume":"111","author":"SM Sirrs","year":"2014","journal-title":"Mol Genet Metab"},{"issue":"15","key":"pone.0325403.ref065","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000006316","article-title":"Enzyme replacement therapy and white matter hyperintensity progression in Fabry disease","volume":"91","author":"JD Stefaniak","year":"2018","journal-title":"Neurology"},{"issue":"1","key":"pone.0325403.ref066","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/mt.2009.220","article-title":"The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease","volume":"18","author":"R Khanna","year":"2010","journal-title":"Mol Ther"},{"issue":"1","key":"pone.0325403.ref067","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2119\/molmed.2015.00088","article-title":"Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease","volume":"21","author":"KM Ashe","year":"2015","journal-title":"Mol Med"},{"issue":"2","key":"pone.0325403.ref068","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10545-013-9643-x","article-title":"Cognitive dysfunction and depression in Fabry disease: a systematic review","volume":"37","author":"FE Bolsover","year":"2014","journal-title":"J Inherit Metab Dis"},{"key":"pone.0325403.ref069","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-62817-2_1","article-title":"What Is Neural Plasticity?","volume":"1015","author":"R von Bernhardi","year":"2017","journal-title":"Adv Exp Med Biol"},{"issue":"4","key":"pone.0325403.ref070","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: Management and treatment recommendations for adult patients","volume":"123","author":"A Ortiz","year":"2018","journal-title":"Mol Genet Metab"},{"key":"pone.0325403.ref071","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ymgme.2022.07.010","article-title":"An expert consensus on practical clinical recommendations and guidance for patients with classic Fabry disease","volume":"137","author":"DP Germain","year":"2022","journal-title":"Mol Genet Metab"},{"issue":"4","key":"pone.0325403.ref072","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70142","article-title":"Quantification of perforant path fibers for early detection of Alzheimer\u2019s disease","volume":"21","author":"Y Uchida","year":"2025","journal-title":"Alzheimers Dement"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T18:24:12Z","timestamp":1763403852000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325403"}},"subtitle":[],"editor":[{"given":"Maria de F\u00e1tima Matos Almeida Henriques de","family":"Macedo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":72,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0325403","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.05.14.654139","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]}}}