title: Early-onset familial lewy body dementia with extensive tauopathy: a clinical, genetic, and neuropathological study.
abstract: We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy bodies, 2 of them starting at age 26 years and the other at 29 years. The father has recently been diagnosed with Lewy body disease, with onset at 77 years. Neuropathological examination of the brain of the index patient disclosed unusual features characterized by diffuse Lewy body disease and generalized neurofibrillary tangle pathology but with no amyloid deposits in any region. Moreover, Lewy body pathology colocalized with neurofibrillary tangles in most affected neurons. Mutation screening that included all coding exons of presenilin 1 (PSEN1), presenilin 2 (PSEN2), alpha-synuclein (SNCA), beta-synuclein (SNCB), microtubule-associated protein tau (MAPT), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and exons 16 and 17 of the amyloid precursor protein (APP) genes did not identify any mutation. Genome-wide single nucleotide polymorphism was performed in 4 family members and ruled out any pathogenic duplication or deletion in the entire genome. In summary, we report a unique family with pathologically confirmed early-onset dementia with Lewy bodies with widespread tau and alpha-synuclein deposition. The absence of mutations in genes known to cause Lewy body disease suggests that a novel locus or loci are implicated in this neurodegenerative disease.
authors.affiliation: Neurology Department, Hospital de la Santa Creu i Sant Pau, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.forename: Laura
authors.initials: L
authors.lastname: Molina-Porcel
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez-Isla
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Cristina
authors.initials: C
authors.lastname: Guardia-Laguarta
authors.forename: Anna
authors.initials: A
authors.lastname: González-Neira
authors.forename: Montserrat
authors.initials: M
authors.lastname: Estorch
authors.forename: Josep
authors.initials: J
authors.lastname: Ma Grau
authors.forename: Lluís
authors.initials: L
authors.lastname: Barraquer
authors.forename: Carles
authors.initials: C
authors.lastname: Roig
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005192:Family Health; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053763:Presenilins / Q000235:genetics / Q000378:metabolism; D024801:Tauopathies / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D053763:Presenilins; D051844:alpha-Synuclein; D016875:tau Proteins