RESUMO
Almost 115 years ago, Alois Alzheimer described Alzheimer's disease (AD) for the first time. Since then, many hypotheses have been proposed. However, AD remains a severe health public problem. The current medical approaches for AD are limited to symptomatic interventions and the complexity of this disease has led to a failure rate of approximately 99.6%in AD clinical trials. In fact, no new drug has been approved for AD treatment since 2003. These failures indicate that we are failing in mimicking this disease in experimental models. Although most studies have focused on the amyloid cascade hypothesis of AD, the literature has made clear that AD is rather a multifactorial disorder. Therefore, the persistence in a single theory has resulted in lost opportunities. In this review, we aim to present the striking points of the long scientific path followed since the description of the first AD case and the main AD hypotheses discussed over the last decades. We also propose insulin resistance as a common link between many other hypotheses.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Encéfalo , Resistência à Insulina/fisiologia , Modelos Biológicos , Doença de Alzheimer/tratamento farmacológico , Amiloide/genética , Amiloide/metabolismo , Biomarcadores , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Descoberta de Drogas , Humanos , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL) rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%). The most common immunophenotype was B lineage (76%). BCR-ABL rearrangements was detected in 14 (34%) patients with the following distribution: p190 (28%), p210 (50%) and double positive (22%). Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44%) and positive BCR-ABL (28%). Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia...
