Open AccessFamilial Dementia With Frontotemporal Features Associated With M146V Presenilin‐1 Mutation
Author(s) -
Riudavets Miguel A.,
Bartoloni Leonardo,
Troncoso Juan C.,
Pletnikova Olga,
St. GeorgeHyslop Peter,
Schultz Marcelo,
Sevlever Gustavo,
Allegri Ricardo F.
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12051
Subject(s) - frontotemporal dementia , proband , presenilin , dementia , pathology , mutation , neuropathology , alzheimer's disease , white matter , medicine , disease , biology , genetics , gene , magnetic resonance imaging , radiology
Abstract Most of the mutations in the presenilin‐1 gene ( PS ‐1) are associated with familial A lzheimer's disease ( AD ). However, certain examples can be associated with frontotemporal dementia ( FTD ). We performed a clinical evaluation of individuals belonging to a family with the FTD phenotype, and additional molecular studies and neuropathological assessment of the proband. The PS ‐1 M146V mutation was found in the 50‐year‐old subject (the proband) with family history of early‐onset FTD . Neuropathological examination showed abundant amyloid plaques, widespread neurofibrillary pathology, P ick bodies in the hippocampus and cortex, cortical globose tangles and ubiquitin‐positive nuclear inclusions in white matter oligodendrocytes. We report a kindred with clinical features of FTD , whose proband bore the PS ‐1 M146V mutation and showed diffuse A lzheimer's type pathology and P ick bodies on post‐mortem neuropathological examination. As with other mutations within the same codon, this substitution may predispose to both diseases by affecting APP and/or tau processing.