The neuropathology associated with the clinical entities frontotemporal dementia (FTD, behavioral variant FTD), progressive non-Xuent aphasia (PNFA) and semantic dementia (SD), is heterogeneous with the common feature being a relatively selective degeneration of the frontal and temporal lobes (frontotemporal lobar degeneration, FTLD). As in other neurodegenerative conditions, most pathological subtypes of FTLD are characterized by specific kinds of intracellular protein inclusions. In the past few decades, the biochemical composition of many of these inclusion bodies has been determined. There is a growing trend to classify FTLD based on the presumed molecular defect, in the belief that this most closely reflects the underlying pathogenic process and because many of the eponymous and descriptively named syndromes of the past are now known to have imperfect clinicopathological correlation.
A comprehensive consensus paper on the neuropathologic diagnostic and nosologic criteria for FTLD was recently published in this journal . These criteria incorporate several important recent advances in our understanding of the molecular genetics and pathology of FTLD; specifically, the discovery of several new FTLD-associated gene abnormalities and the identification of TDP-43 as the pathological protein in most tau-negative FTLD. The criteria employ a protein-based approach for the neuropathologic diagnosis and classification of FTLD; however, the nomenclature for individual conditions has not been revised to reXect this.