Determine the Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker profile in two causes of rapidly progressive dementia (RPD): Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis (AIE).

CJD is a prion-mediated, fatal cause of RPD, while AIE is a potentially treatable cause of RPD that may mimic CJD clinically. AD CSF biomarkers may be measured in RPD to exclude faster than typical AD but utility in discriminating CJD from AIE is not well elucidated.

Twenty-seven patients with RPD received Roche Elecsys AD CSF biomarker testing at Mayo Clinic over one year, including 12 patients with probable or definite CJD and 15 patients with NMDA-R, NIF, LGI1, CASPR2, DPPX, or IgGLON5 antibody-confirmed (9/15) probable or definite AIE. Total-tau (t-tau), phosphorylated-tau (p-tau), and amyloid-β-42 levels were compared using logistic regression.

T-tau was greater in CJD than AIE (OR 1.47, CI 1.19-2.12, p=.0043). T-tau was elevated in 92% of CJD cases (median 970, range 236->1300 pg/mL), of which 50% were above the upper limit of assay measurement; whereas 20% of AIE cases (median 235, range 80->1300 pg/mL) had elevated t-tau, of which all were antibody-negative. Additionally, the t-tau/p-tau ratio was greater in CJD than AIE (OR 2.71, CI 1.56-6.60, p=.0040). The p-tau/amyloid-β-42 ratio was similar in CJD and AIE but lower than reported for AD; 4/12 CJD and 2/15 AIE cases had elevated p-tau/amyloid-β-42 ratios. Age, sex, education, and median disease durations were comparable in RPD patients.

T-tau and t-tau/p-tau ratios were greater in CJD than AIE. The t-tau/p-tau ratio differentiates these causes of RPD. The p-tau/amyloid-β-42 ratio was similar in CJD and AIE.