Homogenous pathology, multifaceted symptomatology

The main conclusion reached with decades of investigation on neurodegeneratives diseases targeting the ATLs is that of a remarkable pathological consistency, yet great heterogeneity of symptoms. On one hand, definitive classification of dementia subtypes and assignment to disease-modifying treatments are based on the underlying neuropathology. As we will see, relative focal atrophy of the ATL makes for strong prediction of TDP-43. On the other hand, the lack of molecular biomarkers forces diagnostic efforts to rely on clinical assessment, possibly supported by neuroimaging findings. With subtle symptoms lying on a spectrum of linguistic, emotional, and behavioral difficulties, early cases are often mis- and underdiagnosed.

The hurdles of diagnostic and classification criteria

Pathological findings and genetic evidence

Structural and Functional Neuroimaging