2022.08.22
Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid
BMJ Neurology Open. 2022;4:e000321. doi:10.1136/bmjno-2022-000321
Kasuga K1, Kikuchi M2,3, Tsukie T1, Suzuki K4, Ihara R5, Iwata A5, Hara N1, Miyashita A1, Kuwano R6, Iwatsubo T7, Ikeuchi T1, the Japanese Alzheimer's Disease Neuroimaging Initiative8
1Molecular Genetics, Niigata University Brain Research Institute
2Genome Informatics, Graduate School of Medicine, Osaka University
3Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo
4Neurology, National Defense Medical College
5Neurology, Tokyo Metropolitan Geriatric Medical Center Hospital
6Asahigawaso Research Institute, Okayama
7Neuropathology, Graduate School of Medicine, The University of Tokyo
8Japanese ADNI, Japan
Abstract
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.
*Reprinted under a CC BY NC ND 4.0 license.
