RESUMO
The neuronal nitric oxide synthase (nNOS) is abundantly expressed in the brain and its transcripts have been found in the frontal cerebral cortex. Eighty-nine patients with different neurodegenerative tau-related disorders, including 71 patients with frontotemporal lobar degeneration (FTLD), 12 with progressive supranuclear palsy (PSP) and 6 with corticobasal degeneration (CBD), were genotyped for the C276T single nucleotide polymorphism (SNP) in exon 29 of the nNOS gene and compared with 190 age-matched controls (CON). A significantly increased allelic frequency of the T allele was observed in patients compared with CON (40.4% vs. 29.7%, P = 0.014, OR: 1.94, CI: 1.15-3.27). Considering each disorder separately, significance was reached for FTLD only (39.4%, P = 0.0248 versus controls, OR: 1.96, CI: 1.11-3.47). However, the frequency of the T allele was elevated also in patients with PSP (45.8%) and CBD (41.7%). No differences were observed stratifying according to gender or apolipoprotein E status. The C276T SNP acts as risk factor for sporadic FTLD, possibly influencing NOS1 transcription. Studies in larger populations are needed to confirm its role in PSP and CBD.
Assuntos
Encéfalo/enzimologia , Demência/enzimologia , Demência/genética , Predisposição Genética para Doença/genética , Óxido Nítrico Sintase Tipo I/genética , Polimorfismo Genético/genética , Idoso , Encéfalo/fisiopatologia , Análise Mutacional de DNA , Demência/fisiopatologia , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Frequência do Gene/genética , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/enzimologia , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Progranulin (PGRN) expression is increased in activated microglia in Alzheimer's disease (AD) brain, suggesting a potential role in this pathology. METHODS: A mutation scanning of exons and flanking regions of PGRN was carried out in 120 patients with sporadic frontotemporal lobar degeneration and 145 with sporadic AD. RESULTS: Amongst variants not yet deposited, a novel allelic variant was identified in Exon 1 (g100169G > A). It leads to an amino acidic change (p.Gly35Arg) and was observed in a patient with late onset AD. In silico analysis predicted that this mutation is possibly damaging. A second variant (g.100165C > T), resulting in a silent mutation (pAsp33Asp), was found in a patient with semantic dementia and in another with early onset AD. Both variants were absent in 226 controls. In addition, two rare non-pathogenic variants lying very close to PGRN splice-site regions (IVS2 + 7-->G > A and IVS7 + 7-->G > A) were observed. Transcriptional analysis in peripheral blood mononuclear cells from patients demonstrated they do not affect exon splicing. CONCLUSIONS: A novel putative PGRN mutation leading to an amino acidic substitution was identified in a patient with clinical AD.
Assuntos
Doença de Alzheimer/genética , Demência/genética , Éxons/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Substituição de Aminoácidos , Estudos de Casos e Controles , Análise Mutacional de DNA , Demência/epidemiologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Progranulinas , Splicing de RNA , Análise de Sequência de DNA , Relação Estrutura-Atividade , Transcrição GênicaAssuntos
Doença de Alzheimer/sangue , Transtornos Cognitivos/sangue , Fatores Etários , Idoso , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Quimiocina CXCL10/sangue , Transtornos Cognitivos/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes NeuropsicológicosRESUMO
OBJECTIVE: To evaluate the cognitive effect of transcranial direct current stimulation (tDCS) over the temporoparietal areas in patients with Alzheimer disease (AD). METHODS: In 10 patients with probable AD, we delivered anodal tDCS (AtDCS), cathodal tDCS (CtDCS), and sham tDCS (StDCS) over the temporoparietal areas in three sessions. In each session recognition memory and visual attention were tested at baseline (prestimulation) and 30 minutes after tDCS ended (poststimulation). RESULTS: After AtDCS, accuracy of the word recognition memory task increased (prestimulation: 15.5 +/- 0.9, poststimulation: 17.9 +/- 0.8, p = 0.0068) whereas after CtDCS it decreased (15.8 +/- 0.6 vs 13.2 +/- 0.9, p = 0.011) and after StDCS it remained unchanged (16.3 +/- 0.7 vs 16.0 +/- 1.0, p = 0.75). tDCS left the visual attention-reaction times unchanged. CONCLUSION: Transcranial direct current stimulation (tDCS) delivered over the temporoparietal areas can specifically affect a recognition memory performance in patients with Alzheimer disease (AD). Because tDCS is simple, safe and inexpensive, our finding prompts studies using repeated tDCS, in conjunction with other therapeutic interventions for treating patients with AD.