Alzheimer's disease biomarker utilization at first referral enhances differential diagnostic precision with simultaneous exclusion of Creutzfeldt‐Jakob disease

Abstract

Most suspected Creutzfeldt‐Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1‐42 (Aβ1‐42), phosphorylated tau 181 (p‐tau181), and total tau (t‐tau) could be assessed via Elecsys immunoassays (n = 419) and NfL via enzyme‐linked immunosorbent assay (ELISA; n = 161). In the non‐CJD sub cohort (n = 371), 59% (219/371) had A+T– (abnormal Aβ1‐42 only) and 21% (79/371) returned A+T+ (abnormal Aβ1‐42 and p‐tau181). In the 48 CJD subjects, a similar AD biomarker profile distribution was observed. To partially address the prevalence of likely pre‐symptomatic AD, NfL was utilized to assess for neuronal damage. NfL was abnormal in 76% (25/33) of A+T– subjects 40 to 69 years of age, 80% (20/25) of whom had normal t‐tau. This study reinforces AD as an important differential diagnosis of suspected CJD, highlighting that incorporating AD biomarkers and NfL at initial testing is worthwhile.

Diagnostic utility of plasma ptau217, ptau181, GFAP for Alzheimer disease in a heterogeneous younger onset dementia clinical cohort

“…CSF profiles were categorised based on the beta amyloid and ptau status, based on the AT(N) framework: A-T-, A-T+, A+T-, A+T+. An A+T+ CSF profile was considered consistent with AD as defined and described earlier, and other AT profiles were groups as 'OtherAT', in keeping with biomarker definitions of AD [23,[26][27][28] and described further in our recent study [29].…”