{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:12:52Z","timestamp":1780063972203,"version":"3.54.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    Alexander disease (ALEXD; MIM 203450) is a rare leukodystrophy caused by dominant mutations in the\n                    <jats:italic toggle=\"yes\">GFAP<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Glial Fibrillary Acidic Protein<\/jats:italic>\n                    ) gene, which encodes a key structural protein of astrocytes. First described in 1949, ALEXD is now recognized as a clinically heterogeneous disorder with a broad phenotypic spectrum spanning neonatal, infantile, juvenile, and adult-onset forms. Clinical manifestations vary according to age at onset and disease subtype, ranging from early developmental impairment and progressive neurologic decline to later-onset presentations dominated by bulbar dysfunction, ataxia, and spinal cord involvement. Diagnosis can be challenging because of phenotypic overlap with other neurologic conditions; however, characteristic magnetic resonance imaging patterns combined with molecular confirmation of\n                    <jats:italic toggle=\"yes\">GFAP<\/jats:italic>\n                    mutations are central to diagnosis. To date, more than 100\n                    <jats:italic toggle=\"yes\">GFAP<\/jats:italic>\n                    mutations have been reported, although robust genotype-phenotype correlations remain elusive. Pathogenic\n                    <jats:italic toggle=\"yes\">GFAP<\/jats:italic>\n                    variants lead to astrocyte dysfunction through protein aggregation, oxidative stress, and cytoskeletal disorganization, resulting in Rosenthal fiber formation. Elevated GFAP levels in cerebrospinal fluid have emerged as a potential biomarker, though their clinical utility remains under investigation. Current management is supportive, but emerging gene-targeted approaches, including antisense oligonucleotides such as zilganersen and AAV-mediated gene silencing strategies, offer promising therapeutic prospects. This review provides an updated overview of the clinical, radiologic, genetic, and molecular features of ALEXD, emphasizing its spectrum of phenotypes across age groups and ongoing efforts toward improved diagnosis and targeted treatment.\n                  <\/jats:p>","DOI":"10.1177\/08830738261422840","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:00:46Z","timestamp":1773669646000},"page":"911-921","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Alexander Disease: A Literature Review for Clinicians"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5034-9582","authenticated-orcid":false,"given":"Maria Tozzo","family":"Pesco","sequence":"first","affiliation":[{"name":"UMass Chan Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xie","sequence":"additional","affiliation":[{"name":"UMass Chan Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora Silvana","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"UMass Chan Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.6.563"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/08830738030180090901"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5706-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-012-1868-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182309f72"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00044-2"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2016-218484"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2011.01268.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1060"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-6056-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.9.1307"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107540"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2025.149388"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.14802\/jmd.23230"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/08830738231210040"},{"key":"e_1_3_2_17_2","unstructured":"Https:\/\/Www.Ncbi.Nlm.Nih.Gov\/Books\/NBK562242\/."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2024-335089"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2025-335863"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20406"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5384-11.2012"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-019-9290-0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-75383-4"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12211"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200270"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.04.004"},{"key":"e_1_3_2_27_2","unstructured":"van der Knaap MS Naidu S Breiter SN et al. 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