CSF Alzheimer's Disease Biomarkers in Relation to Functional Status and Tofersen Treatment Response in ALS

In a real-world retrospective cohort, CSF AD-related biomarkers showed no diagnostic value for distinguishing ALS from other neurodegenerative conditions, while Aβ40, Aβ42, and pTau181 tracked ALSFRS-R and CK-MB.

• Why it matters: The study addresses uncertainty about whether AD-like CSF pathology in ALS has diagnostic or prognostic meaning, and whether it might reflect functional or cognitive status or treatment response.
• What they did: Clinical and CSF biomarker data (Aβ40, Aβ42, t-Tau, pTau181, pNfH, plus serum markers) were analyzed across ALS, AD, Huntington’s disease, and other controls, with longitudinal CSF sampling over one year in three tofersen-treated ALS patients.
• The result: Aβ40, Aβ42, and pTau181 correlated positively with ALSFRS-R global score and serum CK-MB, and a higher Aβ42/Aβ40 ratio was linked to better ECAS memory performance; in tofersen-treated cases, AD-related biomarkers gradually declined during follow-up.