Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States; Alzheimer's Disease and Dementia Research Unit, Biogen Inc., 115 Broadway, Cambridge, MA 02142, United States.
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Curr Opin Neurobiol. 2020 Apr;61:116-124. doi: 10.1016/j.conb.2020.02.003.
Basic research on the biological mechanism of Alzheimer's disease has focused for decades on the age-related aggregation of the amyloid β-protein and its apparent downstream effects on microglia, astrocytes and neurons, including the posttranslational modification of the tau protein that seems necessary for symptom expression. Here, we discuss the highly challenging process of developing disease-modifying therapies and highlight several key areas of current research that are progressing in exciting directions. We conclude that further deep molecular analyses of the disease, including the mechanisms of β-amyloidosis, will enable more effective clinical trials and ultimately achieve the progress that our patients so deserve.
几十年来，针对阿尔茨海默病的生物学机制的基础研究一直集中在与年龄相关的淀粉样 β-蛋白聚集及其对小胶质细胞、星形胶质细胞和神经元的明显下游影响上，包括tau 蛋白的翻译后修饰，这似乎是症状表达所必需的。在这里，我们讨论了开发疾病修饰疗法的极具挑战性的过程，并强调了当前几个正在朝着令人兴奋的方向发展的关键研究领域。我们的结论是，对疾病的进一步深入分子分析，包括β-淀粉样蛋白沉积的机制，将能够使临床试验更有效，并最终取得我们的患者如此期望的进展。
