title: Familial dementia with frontotemporal features associated with M146V presenilin-1 mutation.
abstract: Most of the mutations in the presenilin-1 gene (PS-1) are associated with familial Alzheimer'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, Pick 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 Alzheimer's type pathology and Pick 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.
authors.affiliation: Department of Neuropathology, FLENI, Buenos Aires, Argentina.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Riudavets
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bartoloni
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.forename: Marcelo
authors.initials: M
authors.lastname: Schultz
authors.forename: Gustavo
authors.initials: G
authors.lastname: Sevlever
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Allegri
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics* / Q000473:pathology*; D004569:Electroencephalography; D005192:Family Health; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics*; D013702:Temporal Lobe / Q000473:pathology*; D015898:Tomography Scanners, X-Ray Computed; D014633:Valine / Q000235:genetics
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1; D008715:Methionine; D014633:Valine
keywords: Alzheimer's disease; FTD; M146V; PS-1 mutations; Pick bodies; oligodendrocytes