Application of the AT(N) and Other CSF Classification Systems in Behavioral Variant Frontotemporal Dementia

Abstract

Background: Patients with a frontotemporal lobar degeneration (FTLD) usually manifest with behavioral variant frontotemporal dementia (bvFTD). Alzheimer’s disease (AD) may also manifest with a predominant behavioral-dysexecutive syndrome, similar to bvFTD. Cerebrospinal fluid (CSF) biomarkers, such as total tau (τT), phosphorylated tau (τP-181) and amyloid beta with 42 amino-acids (Aβ42), can predict AD pathology in vivo. The aim of this study was to compare the τT/Aβ42 and τP-181/Aβ42 ratios, the BIOMARKAPD/ABSI criteria and the AT(N) classification system in a cohort of bvFTD patients. Methods: A total of 105 bvFTD patients (21 possible bvFTD; 20%) with CSF data, examined from 2008 to 2022, were included. Seventy-eight AD patients and 62 control subjects were included. The CSF biomarkers were measured with Innotest (2008–2017 subcohort) and EUROIMMUN (2017–2022 subcohort) ELISAs. Results: Depending on the classification system, 7.6 to 28.6% of bvFTD had an AD biochemical profile. The τT/Aβ42 and τP-181/Aβ42 ratios classified more patients as AD compared to the BIOMARKAPD/ABSI and AT(N) systems. The patients with possible bvFTD had higher frequencies of AD compared to the probable bvFTD patients. Conclusions: The four classification criteria of CSF AD biomarkers resulted in differences in AD allocation in this bvFTD cohort. A consensus on the optimal classification criteria of CSF AD biomarkers is pivotal.

Keywords

• behavioral variant
• frontotemporal dementia
• frontotemporal lobar degeneration
• Alzheimer’s disease
• CSF biomarkers
• tau protein