title: BAG1 is a protective factor for sporadic frontotemporal lobar degeneration but not for Alzheimer's disease.
abstract: BCL2-associated athanogene 1 (BAG1) is an anti-apoptotic factor that interacts with tau and regulates its proteasomal degradation. A significant increase of the BAG-1M isoform was found in Alzheimer's disease (AD) brains, and the protein co-localized with tau and amyloid. We carried out an association study of BAG1 in a population of 291 patients clinically diagnosed with frontotemporal lobar degeneration (FTLD), none of whom was a carrier of mutations in progranulin or microtubule associated protein tau genes and 374 with AD as compared with 314 age- and gender-matched controls. In addition, another candidate named Chromatin-modifying protein 5 (CHMP5) and located in the same linkage disequilibrium block, has been included in this study. The distribution of the two single nucleotide polymorphism (SNPs), rs844239 in CHMP5 and rs706118 in BAG1, covering 100% gene variability, were determined. A statistically significant decreased allelic frequency of the BAG-1 rs706118 SNP was observed in patients with FTLD as compared with controls (16.7 versus 23.9%; p = 0.007, OR: 0.35, CI: 0.25-0.50), whereas allelic frequency of the SNP in patients with AD was similar to controls (24.3%, p > 0.05). Conversely, no significant association was found as regards CHMP5 rs844239. Stratifying according to gender, no differences were observed. BAG-1 rs706118 SNP likely acts as protective factor for sporadic FTLD, but not for AD, suggesting its specific role in a pathogenic event in FTLD. Nevertheless, a replication study would be needed to confirm these preliminary results.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Francesca
authors.initials: F
authors.lastname: Clerici
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fumagalli
authors.forename: Elisa
authors.initials: E
authors.lastname: Ridolfi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cappa
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Giordana
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000517:prevention & control; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000517:prevention & control; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors