Frontotemporal dementia is an umbrella clinical term that encompasses a group of neurodegenerative diseases characterised by progressive deficits in behaviour, executive function, or language. Frontotemporal dementia is a common type of dementia, particularly in patients younger than 65 years. The disease can mimic many psychiatric disorders because of the prominent behavioural features. Various underlying neuropathological entities lead to the frontotemporal dementia clinical phenotype, all of which are characterised by the selective degeneration of the frontal and temporal cortices. Genetics is an important risk factor for frontotemporal dementia. Advances in clinical, imaging, and molecular characterisation have increased the accuracy of frontotemporal dementia diagnosis, thus allowing for the accurate differentiation of these syndromes from psychiatric disorders. As the understanding of the molecular basis for frontotemporal dementia improves, rational therapies are beginning to emerge.

ObjectiveBlood‐based biomarkers for neurodegenerative conditions could improve diagnosis and treatment development. Neurofilament light chain (NfL), a marker of axonal injury, is elevated in cerebrospinal fluid (CSF) of patients with progressive supranuclear palsy (PSP). The goal of this study was to determine the diagnostic and prognostic value of plasma NfL in patients with PSP.MethodsPlasma NfL was measured with ultrasensitive digital immunoassay‐based technology at baseline and 1‐year follow‐up in a pilot cohort of 15 PSP patients and 12 healthy controls, and a validation cohort of 147 PSP patients. Mixed linear models tested the ability of plasma NfL to predict neurological, cognitive and functional decline, and brain atrophy.ResultsBaseline mean plasma NfL levels were elevated in PSP patients (31 ± 4 pg/mL, vs. control, 17.5 ± 1 pg/mL, P < 0.05) and this difference persisted at follow‐up. A cutoff value of 20 pg/mL related to the diagnosis of PSP with a sensitivity of 0.80 and specificity of 0.83 (positive likelihood ratio = 4.7 and a negative likelihood radio of 0.24). Patients with higher NfL levels had more severe neurological (PSPRS, −36.9% vs. −28.9%, P = 0.04), functional (SEADL, −38.2% vs. −20%, P = 0.03), and neuropsychological (RBANS, −23.9% vs. −12.3%, P = 001) deterioration over 1 year. Higher baseline NfL predicted greater whole‐brain and superior cerebellar peduncle volume loss. Plasma and CSF NfL were significantly correlated (r = 0.74, P = 0.002).InterpretationPlasma NfL is elevated in PSP and could be of value as a biomarker both to assist clinical diagnosis and to monitor pharmacodynamic effects on the neurodegenerative process in clinical trials.

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