FTD refers to a group of clinical syndromes associated with underlying frontotemporal lobar degeneration (FTLD) pathology. Three major clinical syndromes are recognized: a behavioural variant (bvFTD), which presents with social-emotional dysfunction, and two primary progressive aphasia (PPA) subtypes, the semantic and nonfluent/agrammatic variants.80 A high proportion of FTLD cases present associated motor neuron disease. A third PPA subtype, the logopenic variant, has been included in the recently revised diagnostic criteria,81 although many patients with this variant show underlying AD at autopsy. FTLD pathology, in turn, can be divided into three major molecular classes based on the underlying disease protein: tau (FTLD-tau), TDP-43 (FTLD-TDP), or FUS (FTLD-FUS).80 For some clinical syndromes, such as semantic variant PPA and FTD with motor neuron disease, the underlying FTLD molecular class can be predicted with good confidence during life.82,83 For other syndromes, such as bvFTD, existing criteria do not reliably predict the underlying molecular pathology.83
