Department of Neuropathology, University of Göttingen, Göttingen, Germany.
J Alzheimers Dis. 2012;31(3):651-7. doi: 10.3233/JAD-2012-120856.
Activated microglia is considered to be involved in the progression of Alzheimer's disease (AD). We investigated the effect of amyloid-β(1-40) (Aβ(40) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam(3)CSK(4)) and TLR4 (LPS) on neurons in primary murine neuron-microglia co-cultures. Neuronal viability, assessed by quantifying the number of intact neuronal extensions and their crossings using a newly developed Definiens Cognition Network Technology-based method, was significantly decreased after treatment with Pam(3)CSK(4), LPS, and Aβ(40). Combined treatment with Aβ(40) and Pam(3)CSK(4) or LPS had an additive effect. Hence, in patients with AD, synergistic microglial activation by Aβ and bacterial products during infections might contribute to disease progression.
被激活的小胶质细胞被认为参与了阿尔茨海默病（AD）的进展。我们研究了淀粉样蛋白-β（1-40）（Aβ（40）和 Toll 样受体（TLR）1/2（Pam（3）CSK（4））和 TLR4（LPS）的外源性激动剂对原代鼠神经元-小胶质细胞共培养物中神经元的影响。通过使用新开发的基于 Definiens Cognition Network Technology 的方法定量测量完整神经元延伸的数量及其交叉点，评估神经元活力，在用 Pam（3）CSK（4）、LPS 和 Aβ（40）处理后，神经元活力显著降低。Aβ（40）与 Pam（3）CSK（4）或 LPS 联合治疗具有相加作用。因此，在 AD 患者中，感染期间 Aβ 和细菌产物的协同小胶质细胞激活可能导致疾病进展。
