McGeer P L, Klegeris A, Walker D G, Yasuhara O, McGeer E G
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.
Tohoku J Exp Med. 1994 Nov;174(3):269-77. doi: 10.1620/tjem.174.269.
The beta-amyloid protein deposits of Alzheimer disease, whether in diffuse or consoliated form, are an agglomeration of many extracellular proteins. At least 35 have been reported as components of senile plaques, most of which also occur in diffuse deposits. More than half of these proteins are directly associated with the immune system. Since diffuse deposits are believed to be the precursors of senile plaques, it is important to define the precise molecular events that lead to the transition. Diffuse deposits share with senile plaques the presence of opsonizing components of complement, the complement activators beta-amyloid protein, amyloid P, thrombin, and apolipoprotein E. However, senile plaques contain, in addition, dystrophic neurites, agglomerates of activated microglia, components of the membrane attack complex, and the inhibitors of the membrane attack complex, clusterin, protectin and vitronectin. Microglial cells are professional phagocytes which possess the respiratory burst apparatus when activated. It produces extracellular superoxide molecules which can then form additional toxic products such as hydrogen peroxide and hydroxyl free radicals. It has long been known that opsonized zymosan is a powerful activator of the respiratory burst system. We found this activation could be inhibited by antibodies to complement receptors in the nanomolar range. Dapsone and indomethacin, two antiinflammatory agents that may have therapeutic potential in Alzheimer disease, were weakly inhibitory (10(-4) M range).(ABSTRACT TRUNCATED AT 250 WORDS)
阿尔茨海默病的β-淀粉样蛋白沉积物，无论是弥漫性还是凝聚性形式，都是许多细胞外蛋白质的聚集物。据报道，至少有35种蛋白质是老年斑的组成成分，其中大多数也存在于弥漫性沉积物中。这些蛋白质中一半以上与免疫系统直接相关。由于弥漫性沉积物被认为是老年斑的前体，因此确定导致这种转变的精确分子事件很重要。弥漫性沉积物与老年斑一样，都存在补体的调理成分、补体激活剂β-淀粉样蛋白、淀粉样蛋白P、凝血酶和载脂蛋白E。然而，老年斑还含有营养不良性神经突、活化小胶质细胞的聚集体、膜攻击复合物的成分以及膜攻击复合物的抑制剂、簇集素、保护素和玻连蛋白。小胶质细胞是专业的吞噬细胞，激活时具有呼吸爆发装置。它产生细胞外超氧分子，然后可以形成额外的有毒产物，如过氧化氢和羟基自由基。长期以来已知，调理后的酵母聚糖是呼吸爆发系统的强大激活剂。我们发现这种激活可以被纳摩尔范围内的补体受体抗体抑制。氨苯砜和吲哚美辛这两种可能对阿尔茨海默病具有治疗潜力的抗炎药，抑制作用较弱（10⁻⁴ M范围）。（摘要截短于250字）
