20.500.12556/DiRROS-29696 Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt-Jakob disease with and without concomitant pathologies Introduction: 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. Alzheimer's disease Creutzfeldt–Jakob disease cerebrospinal fluid concomitant pathology neuropathology phosphorylated tau p-tau181 p-tau217 p-tau231 Alzheimerjeva bolezen Creutzfeldt–Jakobova bolezen cerebrospinalna tekočina sočasna patologija nevropatologija fosforiliran tau true false true Angleški jezik Slovenski jezik Neznano 2026-06-03 11:52:01 2026-06-03 11:52:01 2026-06-04 04:04:40 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 5. 7. 2024; str. 5324-5337 iss. 8, [article no.] 13907 Vol. 20 Avg. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8 1552-5279 10.1002/alz.13907 200801283 RAZ_Emersic_Andreja_2024.pdf RAZ_Emersic_Andreja_2024.pdf 1 D9031F3C7ACB542A97CDD90B46A585FF 90fc62e4dd2db97604ef99c3dc18c42ec54d4d2239bdf922849622d1eab6df01 14a3aa47-5f32-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44601 https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.13907 1 e0287747-5f31-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44598 Univerzitetni klinični center Ljubljana 0 0 0