Université Pierre et Marie Curie, Paris VI ; Laboratoire Epsylon, EA-4556, Université Paul Valéry, Montpellier 3, France
Since its seminal characterization, Pick's disease (PiD), was marked by a double ambiguity. Sometimes, with reference to original Pick's descriptions, PiD was macroscopically defined by a circumscribed frontotemporal cerebral atrophy, independently of its causes. Sometimes, on the other hand, it was histologically characterized by absence of Alzheimer pathology and considered as a special form of degenerative process. However, this special degenerative process was defined either by the particular topography of neuronal loss or by specific histological changes, which were described by Alzheimer. Therefore, individualization of PiD and its relationships with Alzheimer's disease have long been controversial, particularly in the United States, despite the clarification provided by French authors in the 1960s, Swiss authors in the 1970s and Swedish and English authors in the 1980s. The term of Frontotemporal dementia (FTD) was choosed by the last authors in 1994 to avoid the debates on the definition of PiD, and to characterize a particular degenerative process without Alzheimer pathology or other diseases. However, the definition and nature of FTD currently remain ambiguous because the term FTD is applied either to clinical syndromes with different presentations according to predominant frontal or temporal atrophy, and regardless of histologic pathology, or to a particular degenerative process, hereditary or sporadic. Notwithstanding neuropathologic and genetic advances in the last decades, significant challenges remain for FTD therapeutic research as a result of the degenerative processes complexity and lack of parallelism between clinical, neuropathological, and genetic data.