Neuroinflammation, neurotransmitter deficits and cortical oscillations impairment in frontotemporal lobar degeneration: implication for innovative therapeutic strategies

Frontotemporal lobar degeneration (FTLD) is an umbrella term used to refer to the set of neuropathologic changes occurring within the cerebral cortex at the frontal and temporal lobes, clinically associated with significant neurological syndromes, often exhibiting some degree of overlap. These syndromes encompass frontotemporal dementia (FTD), a neurodegenerative disorder primarily characterized progressive changes in behavior, deficits of executive function, or language (Bang et al., 2015). The clinical subtypes of FTLD may vary and include the behavioral variant FTD (bvFTD) (Rascovsky et al., 2011), the primary progressive aphasia (PPA) further divided into semantic variant PPA (svPPA), non-fluent variant PPA (nfvPPA) and logopenic variant of PPA (lvPPA) (Gorno-Tempini et al., 2011), and FTD associated with motor neuron disease (FTD-MND). Additionally, FTD-related disorders may comprise corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) (Tsai & Boxer, 2014), both linked to tau-deposition-associated neurodegeneration, which may exhibit signs of frontal lobe dysfunction during their clinical course. In the field of FTD, considerable advancements have been achieved since the initial identification in 1892 by the neurologist Arnold Pick, who described the first patient with progressive speech impairment and left temporal lobe atrophy. Subsequently, since the recognition of intraneuronal inclusions termed "Pick’s bodies" it was to take nearly a century before Mesulam et al. proposed the first diagnostic criteria for FTD language variants and identified the initial three classic clinical presentations of the condition (Mesulam et al., 2012; Brun, 2007). The diagnostic criteria currently employed underwent further refinement in the 2000s.