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

Abstract

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, phosphorylated 181 tau and amyloidβ 42 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-methyld-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 amyloidβ 42 and phosphorylated 181 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.

Systematic approach to diagnosing suspected Creutzfeldt-Jakob disease

“…AD CSF biomarkers are a quick and widely available method to discriminate between AIE and CJD. Total tau in CJD is significantly higher (median >1300 pg/mL) compared with AIE (median 158 pg/mL) 8. Our patient’s total tau on AD biomarker assay was >1300 (electrochemiluminescent immunoassay), which resulted in 2 days after sample collection.…”

Presenile dementia concomitant with Sjogren's syndrome：A Case Report

“…In addition, the patient suffering from "Vitiligo"on her skin, suggesting an autoimmune condition targeting melanocytes in the basal layer of the skin; Coupled with the abnormal TBNK levels, there is justification to consider the presence of "immune abnormalities" may be engaged in the pathogenesis and development of AD / PD in this setting. Which is also known as autoimmune dementia (AiD) [3] . It has been noted that the presence of "immune abnormalities" in patients with dementia is associated with a more rapid and severe decline in cognitive function.…”

Diagnostic Utility of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia

“…By comparison, relatively few studies have considered the diagnostic applications of biomarkers in patients with RPD. Those that have, generally focus on the ability of nonspecific biomarkers of neuroaxonal injury—namely t‐tau and NfL—to differentiate patients with RPD due to prion diseases and neurodegenerative diseases 40,43–47 or other mimics of prion disease, including autoimmune encephalitis 12,48 . Although helpful, the emphasis on nonspecific biomarkers limits diagnostic applications in mixed cohorts and clinical practice.…”