RESUMO
OBJECTIVE: Purposes of this study are: (1) to evaluate attitudes, beliefs and experiences towards dementia among relatives of Italian familial cases; (2) to perform a cross-cultural comparison between Italian and American samples; (3) to identify predictors of intentions to undergo hypothetical genetic testing. METHODS: Participants were 134 relatives of patients affected by familial forms of dementia. We administered tests measuring health psychological styles, social variables, illness perceptions, intentions regarding genetic testing, and perceptions of the pros and cons of genetic testing. RESULTS: Respondents had a poor Alzheimer's disease knowledge and a low perceived dementia threat. When compared to Americans, Italians reported greater willingness to undergo genetic testing and perceived a different subset of benefits and risks. The strongest predictors of test intention were decisional balance, homemaker status and two beliefs concerning dementia causes. CONCLUSIONS: Italians had a poor knowledge of the disease and a low awareness of personal risk of developing dementia. As compared to Americans, they expressed higher intentions to undergo genetic testing and they have a different perception of benefits and risks. PRACTICE IMPLICATIONS: Understanding of cultural differences in knowledge, attitudes and perception of the disease is important to design optimal health services and education programs for dementia.
Assuntos
Atitude Frente a Saúde/etnologia , Demência/etnologia , Família/etnologia , Aconselhamento Genético , Testes Genéticos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Causalidade , Comparação Transcultural , Tomada de Decisões , Demência/diagnóstico , Demência/genética , Feminino , Aconselhamento Genético/métodos , Necessidades e Demandas de Serviços de Saúde , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Motivação , Linhagem , Medição de Risco , Inquéritos e Questionários , Estados UnidosRESUMO
There is now considerable evidence that the gene encoding for tau protein (MAPT) is implicated in frontotemporal dementia (FTD). The role of MAPT haplotypes in neurodegenerative diseases has been suggested, but their contribution in familial dementia has not been extensively investigated. Here, we investigated (1) the association between the MAPT haplotypes and sporadic (sFTD) or familial FTD (FFTD) (controls n = 99, sFTD n = 53, FFTD n = 50), (2) the interactive effect between MAPT haplotypes and APOE gene. We found an overrepresentation of H2 haplotype (OR = 1.83, P = 0.029) and of H2H2 genotype in FFTD patients (OR = 6.09, P = 0.007). This association was even stronger in APOE e4 negatives FFTD (H2: OR = 2.9, P = 0.001; H2H2: OR = 12.67, P = 0.001). Our results support idea that the MAPT H2 haplotype is a risk factor for FFTD. This locus could contain this or other inheritable genetic determinants contributing to increase risk of developing dementia.
Assuntos
Demência/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Proteínas tau/genética , Idoso , Apolipoproteína E4 , Apolipoproteínas E/genética , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Cromossomos Humanos Par 17/genética , Análise Mutacional de DNA , Demência/metabolismo , Demência/fisiopatologia , Feminino , Testes Genéticos , Genótipo , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo Genético/genética , Fatores de Risco , Proteínas tau/metabolismoRESUMO
CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.
Assuntos
Doença de Alzheimer/genética , Cistatinas/genética , Cistatinas/metabolismo , Idoso , Western Blotting , Células Cultivadas , Cistatina C , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Predisposição Genética para Doença , Haplótipos , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Sinais Direcionadores de Proteínas/fisiologia , Pele/citologiaRESUMO
Frontotemporal dementia (FTD) is a clinical entity grouping different diagnostic conditions. FTD can occur in a sporadic form; however in 30-50% of cases a familial form of FTD has been observed. Mutations in the TAU gene were associated to familial FTD linked to chromosome 17. Our aim was to investigated the proportion of FTD cases attributable to TAU gene mutations in an Italian clinical series. We analyzed 38 patients with FTD; of these, 13 had a positive family history of FTD. All TAU gene exons and flanking intronic regions were sequenced. In our familial FTD sample the estimation of TAU gene mutations accounted for a relative low prevalence (7.6%); based on our results we could argue the existence of other mutations in regulatory regions in the TAU gene or, on the other hand, other genes might be responsible for the most cases of familial FTD.
