Alzheimer's disease cerebrospinal fluid biomarkers differentiate patients with Creutzfeldt-Jakob disease and autoimmune encephalitis.

in European journal of neurology by Bryce K Chang, Gregory S Day, Jonathan Graff-Radford, Andrew McKeon, Eoin P Flanagan, Alicia Algeciras-Schimnich, Michelle M Mielke, Aivi Nguyen, David T Jones, Michel Toledano, Walter K Kremers, David S Knopman, Ronald C Petersen, Wentao Li

TLDR

  • This study compared Alzheimer's disease cerebrospinal fluid biomarkers in Creutzfeldt-Jakob disease and autoimmune encephalitis, finding elevated total-tau levels in CJD cases.
  • The results support the use of AD biomarker testing in rapidly progressive dementia diagnosis, potentially improving treatment outcomes.

Abstract

Autoimmune encephalitis (AE) is a potentially treatable cause of rapidly progressive dementia that may mimic Creutzfeldt-Jakob disease (CJD). Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers may discriminate CJD from AD, but utility in discriminating CJD and AE is unclear. This study compared AD CSF biomarkers in CJD and AE. Patients with probable or definite CJD and probable or definite AE who underwent Roche Elecsys AD CSF biomarker testing at Mayo Clinic from March 2020 through April 2021 were included. Total-tau, phosphorylatedtau and amyloid-βlevels were compared. Of 11 CJD cases, four were autopsy proven; the rest had positive real-time quaking-induced conversion testing. Disease-associated autoantibodies were detected in 8/15 cases of AE: leucine-rich glioma-inactivated 1 and neuronal intermediate filaments (two cases each), and N-methyl-d-aspartate receptor, contactin-associated protein-like 2, dipeptidyl-peptidase-like protein 6 and immunoglobulin-like cell adhesion molecule IgLON family member 5. Total-tau provided excellent discrimination between CJD and AE in a univariate model (odds ratio 1.46 per 100 pg/ml, 95% confidence interval 1.17-2.11, p < 0.05, c = 0.93). Total-tau was elevated in 91% of CJD cases (median > 1300, range 236->1300 pg/ml), of which 55% were above the limit of assay measurement (>1300 pg/ml). Total-tau was elevated in 20% of AE cases (median 158, range 80->1300 pg/ml). Total-tau was greater in CJD than AE. Given that amyloid-βand phosphorylatedtau were comparable, the ratio differences were probably driven by elevated total-tau in CJD. This study supports the role for AD biomarker testing in patients with rapidly progressive dementia.

Overview

  • The study investigates the use of Alzheimer's disease cerebrospinal fluid (CSF) biomarkers in distinguishing between Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis (AE).
  • The study includes 11 CJD cases and 15 AE cases, with total-tau, phosphorylatedtau, and amyloid-β levels compared using Roche Elecsys AD CSF biomarker testing.
  • The primary objective is to identify if AD CSF biomarkers can effectively discriminate between CJD and AE and aid in the diagnosis of rapidly progressive dementia.

Comparative Analysis & Findings

  • Total-tau provided excellent discrimination between CJD and AE, with elevated levels in 91% of CJD cases and 20% of AE cases.
  • Amyloid-β and phosphorylatedtau levels were comparable between the two conditions, suggesting that the differences were driven by elevated total-tau in CJD.
  • The ratio differences between CJD and AE were attributed to elevated total-tau in CJD, making it a potential biomarker for distinguishing between the two conditions.

Implications and Future Directions

  • This study supports the role for AD biomarker testing in patients with rapidly progressive dementia, enabling more accurate diagnosis and potentially improved treatment outcomes.
  • Future studies can further investigate the utility of AD CSF biomarkers in differentiating between CJD and AE, particularly in samples from diverse populations.
  • Additional research may also consider exploring the potential application of these biomarkers in other neurodegenerative diseases and their role in monitoring treatment response and disease progression.
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