First Report of Frontotemporal Dementia-Like Phenotype in an Argentine Family with Presenilin-1 M146V Alzheimer's Disease with Pick Bodies

RICARDO F. ALLEGRI, LEONARDO BARTOLONI, CECILIA SERRANO, GALENO ROJAS, MIGUEL RIUDAVETS, GUSTAVO SEVLEVER, ANALIA TARATUTO, PETER ST GEORGE-HYSLOP

Congreso; Annual Meeting American Academy of Neurology; 2010

Background:  Presenilin-1 (PS-1) mutation account for most familial Alzheimer’s disease (AD) and have been reported in familial frontotemporal dementia (FTD). Halliday et al (2005) report a family with a PS-1 M146L mutation and both Pick bodies and AD. Objective: To describe an Argentine Family of FTD-like phenotype with a PS-1 M146V mutation and both Pick bodies and AD. Design and Methods:  A 38-years-old man presented for neurological assessment because of a “frontal behavior” change. His mother had died at 48 years of presenile dementia and two sister were affected. Neuropsychological assessment showed mixed dementia (FTD and AD). MRI revealed frontotemporal atrophy and SPECT reported hypoperfusion in the frontotemporal areas bilaterally. On genetic testing, sequence analysis revealed a heterozygous A>G transition at position 436 of the cDNA (ATG to GTG) leading to an amino acid substitution of methionine (M) to valine (V) at codon 146 in exon 6 of the PS-1 gene.  The patient died 12 years later. At autopsy we found  large number of cortical plaques and NFTs and Pick Bodies. Conclusions: Although the coexistence of AD and FTD pathology is rare, our results indicate an important role for PS-1 in causing various tau pathologies in various cell types and brain localitions. The interactions between neuronal PS-1 and both tau and APP in remodeling suggests an alternate pathway predisposing to FTD/AD pathology in cases with M146V mutations.