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Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our findings suggest an overlap between PLS and AD pathology in <jats:italic>PSEN1<\/jats:italic> variant carriers. Results support considering PLS when diagnosing AD\u2010related motor syndromes and including <jats:italic>PSEN1<\/jats:italic> evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS\u2013AD relationship, informing future treatments and clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Pathogenic variants in presenilin 1 (<jats:italic>PSEN1<\/jats:italic>) can manifest as hereditary primary lateral sclerosis<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>PSEN1<\/jats:italic> Pro284Leu carriers present motor, cognitive, and behavioral alterations\u00a0<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cases had corticospinal tract microgliosis and severe A\u03b2 pathology in motor cortex\u00a0<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>There was no evidence of amyloid deposition in the spinal cord white matter\u00a0<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>All the neuropathology images are available for online visualization\u00a0<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14133","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T15:25:30Z","timestamp":1722093930000},"page":"6384-6394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Primary lateral sclerosis associated with <i>PSEN1<\/i> Pro284Leu variant in a Colombian family: Clinical and neuropathological features"],"prefix":"10.1002","volume":"20","author":[{"given":"Juliana","family":"Acosta\u2010Uribe","sequence":"first","affiliation":[{"name":"Grupo de Neurociencias de Antioquia Universidad de Antioquia  Medell\u00edn Antioquia Colombia"},{"name":"Neuroscience Research Institute and Molecular, Cellular and Developmental Biology Department University of 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