Kasuga Kensaku, Kikuchi Masataka, Tsukie Tamao, Suzuki Kazushi, Ihara Ryoko, Iwata Atsushi, Hara Norikazu, Miyashita Akinori, Kuwano Ryozo, Iwatsubo Takeshi, Ikeuchi Takeshi
Molecular Genetics, Niigata University Brain Research Institute, Niigata, Japan.
Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
BMJ Neurol Open. 2022 Aug 10;4(2):e000321. doi: 10.1136/bmjno-2022-000321. eCollection 2022.
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.
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) and AT(N)). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.
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) and AT(N) classifications. When we used t-tau as the N marker (AT(N)), 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)). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N) and AT(N) classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N) classification, but not in the AT(N) classification.
AT(N) and AT(N) 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.
AT(N)分类法旨在根据生物标志物对个体进行分类。然而，AT(N)特征可能因所选标志物和目标人群的不同而有所差异。
我们根据脑脊液（CSF）生物标志物，对参与日本阿尔茨海默病神经影像学倡议的177名个体进行了AT(N)分类分层。我们比较了使用总tau蛋白和神经丝轻链（NfL）作为N标志物的分类（AT(N)和AT(N)）之间AT(N)特征的频率。对AT(N)特征之间的基线特征、纵向生物学和临床变化进行了检查。
我们发现，在该队列中，9%的认知未受损受试者、49%的轻度认知障碍受试者和61%的阿尔茨海默病（AD）痴呆患者具有生物学AD特征（即A+T+）。AT(N)和AT(N)分类之间的AT(N)特征频率存在显著差异。当我们使用t-tau作为N标志物（AT(N)）时，与使用NfL作为N标志物（AT(N)）相比，T-的个体更常被归类为（N）-，而T+的个体更常被归类为（N）+。在随访期间，在AT(N)和AT(N)分类中，AD连续体组在临床和生物学方面均比正常生物标志物组进展更快。在AT(N)分类的非AD病理变化组中观察到更频繁的痴呆转化，但在AT(N)分类中未观察到。
脑脊液中的AT(N)和AT(N)可能反映神经退行性变的不同方面，并提供不同的预后价值。AT(N)分类有助于理解不同人群中的AD连续体生物学。
