Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt-Jakob disease with and without concomitant pathologiesEmeršič, Andreja (Avtor) Ashton, Nicholas J. (Avtor) Vrillon, Agathe (Avtor) Lantero-Rodriguez, Juan (Avtor) Mlakar, Jernej (Avtor) Gregorič Kramberger, Milica (Avtor) Gonzalez-Ortiz, Fernando (Avtor) Kac, Przemyslaw R. (Avtor) Dulewicz, Maciej (Avtor) Hanrieder, Jörg (Avtor) Rot, Uroš (Avtor) Čučnik, Saša (Avtor) Alzheimer's diseaseCreutzfeldt–Jakob diseasecerebrospinal fluidconcomitant pathologyneuropathologyphosphorylated taup-tau181p-tau217p-tau231Introduction: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p-tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age-related tauopathy (PART) found in Creutzfeldt-Jakob disease (CJD) at autopsy. Methods: We investigated CSF N-terminal p-tau181, p-tau217, and p-tau231 with in-house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post-mortem examination performed in patients with CJD 1.3 (0.3-14.3) months after CSF collection revealed no co-pathology in 10, concomitant AD in 8, PART in 8, and other co-pathologies in 3 patients. Results: N-terminal p-tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t-tau) in the presence of AD and PART co-pathology (rho = 0.758-0.952, p ≤ 001). Concentrations in CJD+AD were indistinguishable from AD dementia, with the largest fold-change in p-tau217 (11.6), followed by p-tau231 and p-tau181 (3.2-4.5). Discussion: Variable fold-changes and correlation with t-tau suggest that p-tau closely associates with neurodegeneration and concomitant AD in CJD. Highlights: N-terminal phosphorylated tau (p-tau) biomarkers are increased in Creutzfeldt-Jakob disease (CJD) with and without concomitant AD. P-tau217, p-tau231, and p-tau181 correlate with total tau (t-tau) and increase in the presence of amyloid beta (Aβ) co-pathology. N-terminal p-tau181 and p-tau231 in Aβ-negative CJD show variation among PRNP genotypes. Compared to mid-region-targeting p-tau181, cerebrospinal fluid (CSF) N-terminal p-tau has greater potential to reflect post-mortem neuropathology in the CJD brain.20242026-06-03 11:52:01Neznano29696UDK: 616.8ISSN pri članku: 1552-5279DOI: 10.1002/alz.13907COBISS_ID: 200801283sl