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

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

Research output: Contribution to journalArticlepeer-review


Background and purpose: 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. Methods: 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, phosphorylated181 tau and amyloid-β42 levels were compared. Results: 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). Conclusion: Total-tau was greater in CJD than AE. Given that amyloid-β42 and phosphorylated181 tau 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.

Original languageEnglish (US)
Pages (from-to)2905-2912
Number of pages8
JournalEuropean Journal of Neurology
Issue number10
StatePublished - Oct 2022


  • Creutzfeldt–Jakob disease
  • autoimmune encephalitis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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