Fluid and Imaging Markers of Frontotemporal Lobar Degeneration

Frontotemporal lobar degeneration (FTLD) consists of a heterogeneous spectrum of pathologies and genetic underpinnings, associated with a spectrum of clinical phenotypes. As a result, reaching a definitive diagnosis, differentiating FTLD from other neurodegenerative disorders with overlapping features, tracking disease progression, and evaluating outcomes in therapeutic trials remain challenging. In this chapter, we review the current knowledge of fluid and imaging biomarkers for FTLD. We discuss markers that have been implemented in clinical practice, including anatomical T1-weighted magnetic resonance imaging (MRI) to evaluate grey matter atrophy, 18F-fluorodeoxyglucose positron emission tomography (PET) imaging which measures regional hypometabolism, and cerebrospinal fluid (CSF) or blood levels of neurofilament light chain as a nonspecific marker for neurodegeneration. We also discuss how combinations of biomarkers may be used to differentiate FTLD from Alzheimer’s disease (AD) or distinguish among different FTLD pathological subtypes. In addition, we discuss several biomarkers that may offer potential as diagnostic or predictive markers in FTLD but need more thorough investigation, such as molecular markers that can distinguish between different types of FTLD pathology or those that reflect common mechanisms in neurodegenerative disorders such as neuroinflammation and synaptic injury. Finally, we review promising developments in the field of FTLD biomarkers and propose the need for a multimodality approach in differential diagnosis and prognostication.