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

Kensaku Kasuga; Tamao Tsukie; Masataka Kikuchi; Takayoshi Tokutake; Kazuo Washiyama; Soichiro Shimizu; Hiroshi Yoshizawa; Yasuko Kuroha; Ryuji Yajima; Hiroshi Mori; Yasuaki Arakawa; Kiyoshi Onda; Akinori Miyashita; Osamu Onodera; Takeshi Iwatsubo; Takeshi Ikeuchi; Japanese Alzheimer’s Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2023.03.007

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

Neurobiol Aging. 2023 Jul:127:23-32. doi: 10.1016/j.neurobiolaging.2023.03.007. Epub 2023 Mar 17.

Authors

Kensaku Kasuga¹, Tamao Tsukie², Masataka Kikuchi³, Takayoshi Tokutake⁴, Kazuo Washiyama⁵, Soichiro Shimizu⁶, Hiroshi Yoshizawa⁷, Yasuko Kuroha⁸, Ryuji Yajima⁹, Hiroshi Mori¹⁰, Yasuaki Arakawa¹¹, Kiyoshi Onda¹², Akinori Miyashita², Osamu Onodera⁴, Takeshi Iwatsubo¹³, Takeshi Ikeuchi¹⁴; Japanese Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan. Electronic address: ken39@bri.niigata-u.ac.jp.
² Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
³ Department of Computational Biology and Medical Sciences, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
⁴ Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
⁵ Department of Neurosurgery, Niigata Rinko Hospital, Niigata, Japan.
⁶ Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan.
⁷ Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
⁸ Department of Neurology, Nishiniigata Chuo Hospital, Niigata, Japan.
⁹ Department of Neurology, Midori Hospital, Niigata, Japan.
¹⁰ Department of Neurosurgery, Sannochou Hospital, Niigata, Japan.
¹¹ Department of Neurosurgery, Joetsu General Hospital, Niigata, Japan.
¹² Department of Neurosurgery, Niigata Neurosurgical Hospital, Niigata, Japan.
¹³ Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁴ Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan. Electronic address: ikeuchi@bri.niigata-u.ac.jp.

PMID: 37030016
DOI: 10.1016/j.neurobiolaging.2023.03.007

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / cerebrospinal fluid
Alzheimer Disease* / diagnosis
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid
Humans
Peptide Fragments / cerebrospinal fluid
Syndrome
tau Proteins / cerebrospinal fluid

Substances

tau Proteins
Biomarkers
Amyloid beta-Peptides
Peptide Fragments