Choi B H, Kim R C, Vaughan P J, Lau A, Van Nostrand W E, Cotman C W, Cunningham D D
Department of Pathology (Neuropathology), University of California, Irvine 92717, USA.
Neurobiol Aging. 1995 Jul-Aug;16(4):557-62. doi: 10.1016/0197-4580(95)00060-r.
A marked and significant reduction of protease nexin-1 (PN-1) and PN-2/amyloid beta protein precursor (A beta PP) was observed in selected regions of Alzheimer's disease (AD) brains as compared to those of aged-matched controls. Correlative analysis indicated a relationship between PN-1 reduction and the severity of pathologic alterations. A statistically significant inverse correlation was noted between the level of PN-1 activity and the density of tau-positive dystrophic neurites in the hippocampus. In view of the ability of thrombin and PN-1 activity to regulate neurite outgrowth, it is possible that abnormal thrombin and PN-1 interactions may play a role in dystrophic neurite formation. The presence of clusters of dystrophic neurites around the capillaries suggests that blood-brain barrier (BBB) dysfunction may enhance such abnormal interactions. The decrease in PN-2/A beta PP levels in AD brains could possibly contribute to neuronal degeneration in AD in view of the ability of PN-2/A beta PP to protect neurons against the toxic effects of the A beta.
与年龄匹配的对照组相比，在阿尔茨海默病（AD）大脑的特定区域观察到蛋白酶连接素-1（PN-1）和PN-2/淀粉样β蛋白前体（AβPP）显著且明显减少。相关性分析表明PN-1减少与病理改变的严重程度之间存在关联。在海马体中，PN-1活性水平与tau阳性营养不良性神经突密度之间存在统计学上显著的负相关。鉴于凝血酶和PN-1活性调节神经突生长的能力，异常的凝血酶与PN-1相互作用可能在营养不良性神经突形成中起作用。毛细血管周围存在营养不良性神经突簇表明血脑屏障（BBB）功能障碍可能会增强这种异常相互作用。鉴于PN-2/AβPP保护神经元免受Aβ毒性作用的能力，AD大脑中PN-2/AβPP水平的降低可能导致AD中的神经元变性。
