Laboratory of Cellular and Molecular Neurosciences, Faculty of Sciences, University of Chile & International Center for Biomedicine (ICC), Edificio Milenio, Las Encinas, Nuñoa, Santiago, Chile.
Arch Med Res. 2010 Apr;41(3):226-31. doi: 10.1016/j.arcmed.2010.03.007.
Many hypotheses have been raised regarding the pathophysiology of Alzheimer's disease (AD). Because amyloid beta peptide (Abeta) deposition in senile plaques appears as a late, nonspecific event, recent evidence points to tau phosphorylation and aggregation as the final common pathway in this multifactorial disease. Current approaches that provide evidence in favor of neuroimmunomodulation in AD and the roles of tau pathological modifications and aggregation into oligomers and filamentous forms are presented. We propose an integrative model on the pathogenesis of AD that includes several damage signals such as Abeta oligomers, oxygen free radicals, iron overload, homocysteine, cholesterol and LDL species. These activate microglia cells, releasing proinflammatory cytokines and producing neuronal degeneration and tau pathological modifications. Altered and aggregated forms of tau appear to act as a toxic stimuli contributing to neurodegeneration. Recent findings provide further support to the central role of tau in the pathogenesis of AD, so this protein has turned into a diagnostic and therapeutic target for this disease.
许多假说已经提出了阿尔茨海默病（AD）的病理生理学。由于淀粉样β肽（Abeta）在老年斑中的沉积似乎是一个晚期的、非特异性的事件，最近的证据表明，tau 磷酸化和聚集是这种多因素疾病的最终共同途径。目前的方法提供了神经免疫调节在 AD 中的证据，以及 tau 病理修饰和聚集到寡聚体和丝状形式的作用。我们提出了一个 AD 发病机制的综合模型，包括 Abeta 寡聚体、氧自由基、铁过载、同型半胱氨酸、胆固醇和 LDL 等几种损伤信号。这些信号激活小胶质细胞，释放促炎细胞因子，并导致神经元变性和 tau 病理修饰。改变和聚集的 tau 形式似乎作为一种毒性刺激物，导致神经退行性变。最近的发现进一步支持了 tau 在 AD 发病机制中的核心作用，因此这种蛋白已成为该疾病的诊断和治疗靶点。
