NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE Atypical Huntington’s disease with the clinical presentation of behavioural variant of frontotemporal dementia Stanislav Sutovsky 1 • Tomas Smolek 2 • Irina Alafuzoff 3 • Andrej Blaho 1 • Vojtech Parrak 2,6 • Peter Turcani 1 • Michal Palkovic 4 • Robert Petrovic 5 • Michal Novak 2 • Norbert Zilka 2,6 Received: 27 April 2016 / Accepted: 24 May 2016 Ó Springer-Verlag Wien 2016 Abstract Huntington’s disease is an incurable, adult-on- set, autosomal dominant inherited disorder caused by an expanded trinucleotide repeat (CAG). In this study, we describe a Huntington’s disease patient displaying clinical symptoms of the behavioural variant of frontotemporal dementia in the absence of tremor and ataxia. The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trin- ucleotide CAG repeats in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neu- ropathological assessment revealed extensive amyloid b (Ab) aggregates in all cortical regions. No inclusions dis- playing hyperphosphorylated tau or phosphorylated trans- active response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. Confocal microscopy revealed that the majority of p62 intranuclear lesions co-localised with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington’s disease. The presented proband suffered from Huntington’s disease showed atypical dis- tribution of FUS positive intranuclear aggregates in the cortical areas with concomitant Alzheimer’s disease pathology. Keywords Behavioural variant FTD Á FUS Á Huntingtin Á Intranuclear inclusions Á Amyloid Introduction Huntington’s disease (HD) is an inherited neurodegenera- tive disorder characterised by progressive motor, cognitive and psychiatric symptoms. It is caused by an expanded trinucleotide repeat (CAG) repeat within the Huntington’s gene on chromosome 4 and is inherited in an autosomal dominant manner. Symptoms usually progress over 15–20 years. Currently, there are no disease-modifying therapies available (Ghosh and Tabrizi 2015). Previously, it has been shown that HD may be part of the clinical spectrum of the behavioural variant of fron- totemporal dementia phenotype (bv-FTD). Nielsen and colleagues described two cases presenting with involuntary choreathetoid movements and the behavioural changes characteristic for bv-FTD (Nielsen et al. 2010). It is note- worthy that they did not detect any trinucleotide repeat expansion of Huntingtin in the reported cases. Moreover, Doi and co-authors demonstrated that poly-Q aggregates co-localised with the fused-in-sarcoma protein (FUS) in a cellular and mouse model (R6/2) of HD (Doi et al. 2008). & Norbert Zilka norbert.zilka@savba.sk 1 Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic 2 Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska 9, 845 10 Bratislava, Slovak Republic 3 Department of Immunology, Genetics and Pathology, Department of Clinical Pathology, Uppsala University Hospital, Uppsala University, Uppsala, Sweden 4 Department of Pathological Anatomy, Commenius University, Bratislava, Slovak Republic 5 Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Commenius University, Bratislava, Slovak Republic 6 Institute of Neuroimmunology, n.o., Bratislava, Slovak Republic 123 J Neural Transm DOI 10.1007/s00702-016-1579-5