The clinical application of optimized AT(N) classification in Alzheimer's clinical syndrome (ACS) and non-ACS conditions

Abstract

We aimed to assess the utility of AT(N) classification in clinical practice. We measured the cerebrospinal fluid levels of amyloid-β (Aβ) 42, Aβ40, phosphorylated tau, total tau, and neurofilament light chain (NfL) in samples from 230 patients with Alzheimer's clinical syndrome (ACS) and 328 patients with non-ACS. The concordance of two A-markers (i.e., Aβ42 alone and the Aβ42/Aβ40 ratio) 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 (i.e., total tau and NfL) was 40.4% in the ACS group and 24.4% in the non-ACS group. In the ACS samples, the frequency of biological Alzheimer's disease (i.e., A+T+) in N_tau+ cases was 95% while that in N_NfL+ cases was 65%. Reflecting Aβ deposition and neurodegeneration more accurately, we recommend the use of AT(N) classification defined by cerebrospinal fluid A_Aβ-ratioTN_NfL in clinical practice.

Keywords: AT(N) classification; Alzheimer’s clinical syndrome; Aβ42/Aβ40 ratio; Biomarker; Cerebrospinal fluid (CSF); Neurofilament light (NfL).