RESUMO
ADAM10 is a potential biomarker for Alzheimer's disease (AD). ADAM10 protein levels are reduced in platelets of AD patients. The aim was to verify the total blood and platelet ADAM10 gene expression in AD patients and to compare with mild cognitive impairment (MCI) and healthy subjects. No significant differences in ADAM10 gene expression were observed. Therefore, the decrease of ADAM10 protein in platelets of AD patients is not caused by a reduction in ADAM10 mRNA. Further studies must be performed to investigate other pathways in the down regulation of ADAM10 protein.
Assuntos
Proteínas ADAM/genética , Doença de Alzheimer/sangue , Secretases da Proteína Precursora do Amiloide/genética , Disfunção Cognitiva/sangue , Proteínas de Membrana/genética , RNA Mensageiro/genética , Proteínas ADAM/sangue , Proteína ADAM10 , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Secretases da Proteína Precursora do Amiloide/sangue , Biomarcadores/sangue , Plaquetas/metabolismo , Plaquetas/patologia , Estudos de Casos e Controles , Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Feminino , Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Testes Neuropsicológicos , RNA Mensageiro/sangueRESUMO
Alzheimer's disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis.
Assuntos
Proteínas ADAM/sangue , Doença de Alzheimer/sangue , Secretases da Proteína Precursora do Amiloide/sangue , Biomarcadores/sangue , Plaquetas/metabolismo , Proteínas de Membrana/sangue , Proteína ADAM10 , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Western Blotting , Brasil/epidemiologia , Interpretação Estatística de Dados , Manual Diagnóstico e Estatístico de Transtornos Mentais , Escolaridade , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Masculino , Caracteres SexuaisRESUMO
BACKGROUND: Previous studies have demonstrated a decrease in platelet ADAM10 expression among patients with Alzheimer's disease (AD) and healthy matched subjects. The association between cognitive tests and molecular biomarkers, such as platelet ADAM10, may contribute to an accurate AD diagnosis. OBJECTIVE: The aim of this research was to investigate whether cognitive deficits in AD, assessed by Mini-Mental State Exam (MMSE), correlate with ADAM10 platelet levels and if that contributes to a more effective AD diagnosis. METHODS: Elderly patients with probable AD (n = 30) and a non-AD control group (n = 25), matched by age, gender, and education level were evaluated. Platelet proteins were analyzed on SDS-PAGE (10%) and ADAM10 expression was identified by western blotting. ß-actin was used as the endogenous control. The Spearman correlation coefficient between ADAM10 and MMSE ratio was obtained for each group. RESULTS: The MMSE ratio of AD subjects (0.45 ± 0.32) was significantly different (p < 0.001) compared to the non-AD group (1.14 ± 0.07). The relationship between MMSE ratio and ADAM10 expression was significant (r = 0.62, p = 0.0003) for the AD group. The combination of ADAM10 and MMSE at a cutoff ≤ 0.87 presented a sensitivity of 85%, and a specificity of 97% (AUC 0.99, 95% CI 0.92 -1.00), which was significantly better for AD diagnosis than the AUCs of MMSE (p = 0.05) and ADAM10 expression (p = 0.18) separately. CONCLUSIONS: The association of MMSE and ADAM10 expression was significantly better compared with MMSE and ADAM10 expression separately, thus providing and additional diagnostic tool for AD.