Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid

BACKGROUND: The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population. METHODS: We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)(tau) and AT(N)(NfL)). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles. RESULTS: We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)(tau) and AT(N)(NfL) classifications. When we used t-tau as the N marker (AT(N)(tau)), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)(NfL)). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)(tau) and AT(N)(NfL) classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)(tau) classification, but not in the AT(N)(NfL) classification. CONCLUSIONS: AT(N)(tau) and AT(N)(NfL) in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.