Abstract
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.
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This post is Copyright: Andreja Emeršič,
Nicholas J. Ashton,
Agathe Vrillon,
Juan Lantero‐Rodriguez,
Jernej Mlakar,
Milica Gregorič Kramberger,
Fernando Gonzalez‐Ortiz,
Przemysław R. Kac,
Maciej Dulewicz,
Jörg Hanrieder,
Eugeen Vanmechelen,
Uroš Rot,
Henrik Zetterberg,
Thomas K. Karikari,
Saša Čučnik,
Kaj Blennow | June 25, 2024