{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:13:16Z","timestamp":1790399596857,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014012","name":"FightMND","doi-asserted-by":"publisher","award":["IM\u2010202303\u201000957"],"award-info":[{"award-number":["IM\u2010202303\u201000957"]}],"id":[{"id":"10.13039\/100014012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by the degeneration of motor neurons and the presence of TAR DNA\u2010binding protein 43 (TDP\u201043) aggregation in the brain. Dyslipidemia is a common feature of ALS, and increasing evidence indicates that lipid dysregulation in the central nervous system underlies ALS pathology. Sphingomyelin is a sphingolipid that is highly enriched in the human brain. However, very little is known about changes in sphingomyelin in the context of ALS brain. We therefore undertook a comprehensive analysis of sphingomyelin in the disease\u2010affected motor cortex and disease\u2010unaffected cerebellum in sporadic ALS with TDP\u201043 pathology using liquid chromatography\u2010mass spectrometry. We found that sphingomyelin was significantly increased in the ALS motor cortex compared to controls and was strongly associated with disease duration. In contrast, sphingomyelin was unaltered in the cerebellum. The increase in sphingomyelin was associated with an upregulation of ATP\u2010binding cassette subfamily A member 8 (ABCA8), a sphingomyelin transporter, only in the motor cortex of ALS. Importantly, both sphingomyelin and ABCA8 were associated with TDP\u201043 only in the motor cortex. These results suggest that increases in sphingomyelin and ABCA8 could be a protective response against TDP\u201043 pathology.<\/jats:p>","DOI":"10.1111\/bpa.70053","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T02:11:20Z","timestamp":1763950280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Upregulation of sphingomyelin and\n                    <scp>ABCA8<\/scp>\n                    in response to\n                    <scp>TDP<\/scp>\n                    \u201043 pathology in amyotrophic lateral sclerosis brain"],"prefix":"10.1111","volume":"36","author":[{"given":"Finula I.","family":"Isik","sequence":"first","affiliation":[{"name":"Brain and Mind Centre The University of Sydney  Sydney New South Wales Australia"},{"name":"School of Medical Sciences The University of Sydney  Sydney New South Wales 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