First report of frontotemporal dementia-like phenotype in an argentine family with presenilin-1 M146V Alzheimer's disease with Pick Bodies.

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. To describe an Argentine Family of FTD-like phenotype with a PS-1 M146V mutation and both Pick bodies and AD. 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 and pontine “cotton wool” plaques with NFTs, FT cortical Pick Bodies, TAU and ubiquitine positive in hippocampus. 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 the first report with M146V mutations in Argentine. 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 the first report with M146V mutations in Argentine.