DOI: 10.1002/alz.072618 ISSN: 1552-5260

AT(N) Classification and Clinical Characterization by CSF Biomarkers in Patients with Corticobasal Syndrome

Takanobu Ishiguro, Kensaku Kasuga, Takayoshi Tokutake, Tamao Tsukie, Takuya Konno, Osamu Onodera, Takeshi Ikeuchi
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Corticobasal syndrome (CBS) is clinically characterized by asymmetric cortical and extrapyramidal deficits. CBS is caused by various pathological conditions including primary tauopathy and Alzheimer’s disease (AD). To clarify whether there are differences in clinical features of CBS between AD pathology and non‐AD pathology, we classified CBS patients based on AT(N) system by cerebrospinal fluid (CSF) biomarkers and assessed the clinical characteristics of the classified groups.


We assessed retrospectively 19 CBS patients (7 males and 12 females) diagnosed by neurologists at our hospital between 2014 to 2021. They all fulfilled the clinical symptoms of probable or possible CBS according to the Armstrong criteria of corticobasal degeneration. CSF AT(N) biomarkers, A marker: Aβ42 and Aβ42/Aβ40 ratio, T marker: phosphorylated tau (Thr181) [p‐tau], N marker: total tau [t‐tau] and neurofilament light chain [NfL], were evaluated. The positive/negative of each biomarker was judged according to the cutoff value calculated in a cohort independent of this study. We used Aβ42/Aβ40 ratio as the A marker and NfL as the N marker in this study. Each patient was classified AT(N) group. Clinical characteristics were compared between biological AD (i.e., A+T+) group and non‐AD group.


The concordance of A markers (Aβ42 and Aβ42/Aβ40 ratio) was 68.4%, and that of N markers (t‐tau and NfL) was 15.8% in patients with CBS. NfL had more positive rates than t‐tau in CBS patients. Based on CSF biomarker profile, CBS patients were classified as AD group (n = 4, 21%), Alzhehimer’s and concomitant suspected non‐Alzheimer’s pathologic change group (n = 2, 11%) and non‐AD pathologic change group (n = 13, 68%). AD group showed lower scores of MMSE (p = 0.037), more frequent presence of Gerstmann syndrome (p = 0.007), predominance of right limb symptoms (p = 0.015), and more common in non‐motor symptoms onset (p = 0.029) than non‐AD group.


By applying the AT(N) classification to CBS patients, we found that 21% of patients exhibited AD pattern by CSF biomarkers. The clinical differences between AD group and non‐AD group may reflect the different pathological backgrounds. NfL could be more sensitive than t‐tau as the N marker in detecting neurodegeneration of CBS.

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