FTD-GRN is a rapid progression disorder. Hence, it is important to model the cascade of biomarkers for understanding the disease’s etiology and for monitoring the mutation carriers. This study aims to estimate the FTD-GRN biomarker changes.
The study included 35 symptomatic and 56 pre-symptomatic GRN mutation carriers. It also had 35 healthier subjects. NfL, white matter microstructure, grey matter volume, and cognitive domains are the selected biomarkers. The event-based modeling helped to infer the biomarker changes via cross-validation. The researchers used behavioral variant FTD and nfvPPA for understanding the phenotypes.
The first primary abnormal biomarkers were NfL and language functioning. The white matter tracts had changes before the grey matter volume. The degeneration occurs in the left hemisphere before the right. There is a strong correlation between the functional severity and disease severity in nfvPPA, and not in the behavioral variant. There might be a delineation of presymptomatic and symptomatic carriers based on the severity of the disease. The biomarker cascade in nfvPPA shows less uncertainty than the other.
The earliest biomarkers are language deficits and axon degeneration for FTD-GRN. The behavioral variant FTD has a heterogeneous progression of the disease. This data-derived model will help in identifying pre-symptomatic carriers that are at the risk of conversion.
Ref URL: https://jnnp.bmj.com/content/early/2021/01/15/jnnp-2020-323541
