Blood-Based Biomarkers in Frontotemporal Dementia: A Narrative Review

Abstract

This narrative review explores the current landscape of blood biomarkers in Frontotemporal dementia (FTD). Neurofilament light chain (NfL) may be useful in the differentiation of behavioral variant FTD from primary psychiatric disorders (PPDs) or dementia with Lewy bodies (DLB). In prodromal FTD and presymptomatic mutation carriers (GRN, MAPT, C9orf72), elevated NfL may herald pheno-conversion to full-blown dementia. Baseline NfL correlates with steeper neuroanatomical changes and cognitive, behavioral and functional decline, making NfL promising in monitoring disease progression. Phosphorylated neurofilament heavy chain (pNfH) levels have a potential limited role in the demarcation of the conversion stage to full-blown FTD. Combined NfL and pNfH measurements may allow a wider stage stratification. Total tau levels lack applicability in the framework of FTD. p-tau, on the other hand, is of potential value in the discrimination of FTD from Alzheimer's dementia. Progranulin concentrations could serve the identification of GRN mutation carriers. Glial fibrillary acidic protein (GFAP) may assist in the differentiation of PPDs from behavioral variant FTD and the detection of GRN mutation carriers (additional research is warranted). Finally, TAR DNA-binding protein-43 (TDP-43) appears to be a promising diagnostic biomarker for FTD. Its potential in distinguishing TDP-43 pathology from other FTD-related pathologies requires further research.

Keywords: TAR DNA-binding protein-43; glial fibrillary acidic protein; neurofilament light chain; p-tau; phosphorylated neurofilament heavy chain; progranulin; tau.