Application of AT(N) Classification Using Two CSF A‐markers and Two CSF N‐markers to Alzheimer’s Clinical Syndrome (ACS) and Non‐acs

Background Cerebrospinal fluid (CSF) biomarkers reflect the pathological process underlying Alzheimer’s disease (AD) and improve the accuracy of AD diagnosis. AT(N) classification using these CSF biomarkers has been used within the research framework to identify points on AD continuum. However, there has been little research into the utility of AT(N) classification in clinical practice. Methods We measured the CSF levels of amyloid‐β (Aβ) 42, Aβ40, phosphorylated tau (Thr181), total tau (tTau), and neurofilament light chain (NfL) in samples from clinical cases, comprising 230 patients with Alzheimer’s clinical syndrome (ACS) and 328 patients with non‐ACS. The concordance between two A‐markers (i.e., Aβ42 alone and the Aβ42/Aβ40 ratio) and the two N‐markers (i.e., tTau and NfL) were analyzed. We evaluated the prevalence of biological AD (i.e., A+T+) and the percentage of each AT(N) category identified using the CSF biomarkers in the ACS and non‐ACS samples. Results The concordance of A‐markers was not significantly different between the ACS (87.4%) and non‐ACS (74.1%) groups. However, the frequency of discordant cases with A Aβ42‐alone +/A Aβ‐ratio − was significantly higher in the non‐ACS (23.8%) than in the ACS group (7.4%). The concordance of two N‐markers was 40.4% in the ACS group and 24.4% in the non‐ACS group. In the ACS samples, the frequency of biological AD in N tau + cases was 95% and that in N NfL + cases was 65%. When the Aβ42/Aβ40 ratio was used as the A‐marker, the proportion of biological AD was 64.3% in ACS samples and 24.4% in non‐ACS samples. Notably, the proportion of AD continuum in the non‐ACS group was substantially different when the A‐marker was Aβ42 alone than when it was the Aβ42/Aβ40. Conclusions Although the AT(N) classification system was intended for use in research, it may also be also useful for clinical diagnosis. As an A‐marker, the Aβ42/Aβ40 ratio reflects Aβ deposition more accurately than Aβ42 alone. As an N‐marker, NfL reflects neurodegeneration more accurately than tTau, particularly in non‐ACS patients. Thus, we recommend the use of AT(N) classification in clinical practice that is defined by CSF levels of A Aβ‐ratio TN NfL.