Multimarker panels in FTD
Frontotemporal dementia is the most common cause of early-onset dementia and the principal cause of FrontoTemporal Lobular Degeneration (FTLD). Approximately, 90–95% of FTLD cases are characterized by the accumulation in the brain of two different proteins – tau and transactive response DNA-binding protein-43 (TDP-43). These protein inclusions lead to a loss of neural connections (synapses), cellular dysfunction, and eventually, to the death of neurons. In our recent study, entitled “Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration” we showed for the first time, a relationship between cerebrospinal fluid (CSF) levels of synaptic proteins with the abundance of TDP-43 inclusions in the brain and the degree of cognitive impairment in a cohort of patients with FTLD. The study was published in the journal entitled Molecular Neurodegeneration.
What have we done in this study?
In this study, we compared CSF levels of 8 synaptic proteins in a cohort of FTLD and Alzheimer’s disease patients as well as cognitively healthy controls recruited from the Penn FTD Center and Alzheimer’s Disease Research Center (ADRC) at the University of Pennsylvania (Philadelphia, USA). The objective of the study was to determine the relationship of antemortem CSF levels of the synaptic proteins with the abundance of tau and TDP-43 inclusions quantified at autopsy and with cognitive performance.
The main finding of this work, led by Alba Cervantes and Dr. Olivia Belbin, was that FTLD patients had lower CSF concentrations of two synaptic proteins (calsyntenin-1 and neurexin-2a) compared to Alzheimer’s disease patients and controls. Furthermore, low CSF concentrations were associated with increased abundance of TDP-43 inclusions post-mortem. We also found that the combined concentrations of multiple synaptic proteins (including calsyntenin-1) were associated with worse cognitive performance in FTLD patients and showed improved diagnostic performance to distinguish patients with Tau or TDP inclusions.
Relevance of the study
These synaptic panels have potential in the differential diagnosis of FTLD subtypes and as surrogate markers of cognitive performance in future clinical trials targeting TDP-43 or tau.
Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration. Cervantes González, A, Irwin, DJ, Alcolea, D et al. Mol Neurodegener 2022