{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:03:31Z","timestamp":1790046211687,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) share neuropathological features, including tau, amyloid, and TDP\u201043 pathology. This study investigated whether AD\u2010related pathological changes are associated with cognitive impairment ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cerebrospinal fluid (CSF total\u2010tau, phosphorylated\u2010tau, beta\u2010amyloid) and plasma biomarkers (TDP\u201043; neurofilament light chain [NfL]) were analyzed in 192 individuals with ALS or ALS with frontotemporal dementia (ALS\u2010FTD) and 100 healthy controls. Cognitive performance was assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Group comparisons and regression analyses examined associations between biomarker profiles and cognitive status. Autopsy data were available for a subset of participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with healthy controls, patients with ALS \u2013 particularly those with cognitive impairment (ALSci) or ALS\u2010FTD \u2013 showed elevated AD\u2010related biomarkers. Significant differences in beta\u2010amyloid levels were observed between healthy controls (HCs) and patients with ALSci, but not between controls and cognitively unimpaired patients. CSF p\u2010tau and total\u2010tau levels were strongly associated with domain\u2010specific cognitive performance. In contrast, plasma extracellular vesicle TDP\u201043 and NfL showed weak or no association with cognition. In vivo biomarkers alone reliably distinguished cognitive impairment only in ALSci and ALS\u2010FTD. Postmortem analyses showed no strong association between ABC scores or overall TDP\u201043 burden and cognitive state; however, temporal and hippocampal TDP\u201043 burden was associated with cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our findings suggest that tau\u2010related CSF biomarkers, particularly p\u2010tau and total\u2010tau, are associated with cognitive deficits in ALS, indicating that AD\u2010related pathology might be associated to cognitive decline in ALS. However, postmortem data showed even stronger relation of TDP43 pathology to cognitive deficits in ALS. 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