ORIGINAL ARTICLE CSF metabolites in the differential diagnosis of Alzheimer’s disease from frontal variant of frontotemporal dementia Francesca de Rino • Filippo Martinelli-Boneschi • Francesca Caso • Marta Zuffi • Matteo Zabeo • Gabriella Passerini • Giancarlo Comi • Giuseppe Magnani • Massimo Franceschi Received: 3 August 2011 / Accepted: 18 November 2011 / Published online: 29 November 2011 Ó Springer-Verlag 2011 Abstract The early differentiation between Alzheimer’s disease (AD) and frontal variant of frontotemporal dementia (fvFTD) is frequently difficult, albeit critical for the adequate management of patients and their caregivers. In order to assess the accuracy of CSF levels of beta- amyloid 1–42 (Ab), tau (s) and Thr 181-phosphorilated tau (Ps) in the early differentiation of AD from fvFTD, we designed a prospective study in which patients have been followed up for at least 2 years. Seventy-two patients with AD and 42 patients with fvFTD showed significantly dif- ferent CSF levels of Ps (increased in AD, p = 0.0001), Ab (reduced in AD, p = 0.03), and ratios of Ps to Ab (p = 0.003). ROC analyses showed that the ratio Ps/Ab is able to predict diagnosis with an AUC of 0.73 (optimal level being 0.16) corresponding to a sensitivity of 80% and a specificity of 68%. Our findings suggest that CSF metabolites may be the important tools in the early dif- ferential diagnosis between AD and fvFTD, albeit to be correlated with clinical, neuropsychological and bio imaging features. Keywords Alzheimer’s disease  Frontotemporal dementia  CSF  Beta-amyloid  Tau protein  Phospho-tau Introduction The nosographical diagnosis of dementia may be difficult in some specific situations. It is well known that dominant hippocampal amnesia associated with perceptuo-spatial problems in the presence of preserved social skills suggests Alzheimer’s disease (AD). On the contrary, a breakdown of social behaviour, executive skills and/or language function in the presence of preserved memory function favours the diagnosis of frontotemporal dementia (FTD). Alzheimer’s disease is the prevalent type of dementia in the elders, while FTD is the prevalent type of dementia under the age of 60 [1]. However, it is increasingly rec- ognized that tardive forms of FTD are not uncommon. On the other hand, the existence of ‘‘atypical’’ variants of AD is now well recognized [2]; for example an early language disorder might be confused with progressive aphasia of FTD or behavioural disorders might address the diagnosis towards FTD. Consequently the early differentiation between AD and FTD may be difficult, particularly in cases of frontal var- iant FTD (fvFTD), mainly characterized by dysexecutive deficits and behavioural disorders. However, an early differentiation between these two forms is critical for the management of patients and their caregivers for several reasons. First, symptomatic treatments are available only for AD patients, though costly and not without side effects. F. de Rino  M. Zuffi  M. Franceschi (&) Department of Neurology, IRCCS Multimedica, Milan, Italy e-mail: massimo.franceschi@multimedica.it F. Martinelli-Boneschi  F. Caso  G. Comi  G. Magnani Institute of Experimental Neurology (INSPE), Vita-Salute S.Raffaele University, Milan, Italy F. Martinelli-Boneschi  G. Comi  G. Magnani Department of Neurology, IRCCS S.Raffaele, Milan, Italy M. Zabeo Multilab, Multimedica, Milan, Italy G. Passerini Laboraf, IRCCS San Raffaele, Milan, Italy 123 Neurol Sci (2012) 33:973–977 DOI 10.1007/s10072-011-0866-z