Ghiso J, Tagliavini F, Timmers W F, Frangione B
Department of Pathology, New York University Medical Center, New York 10016.
Biochem Biophys Res Commun. 1989 Aug 30;163(1):430-7. doi: 10.1016/0006-291x(89)92154-2.
The amyloid fibrils deposited in cerebral vessel walls and senile plaques in Alzheimer's disease are polymeric forms of a 4 kDa fragment produced by proteolysis of a putative precursor protein (APP). Using antibodies to several fragments of the deduced precursor, we were able to demonstrate the presence of APP in senile plaques, brain extracts and cerebrospinal fluid. Membrane-associated APP is detected as a group of 105-135 kDa proteins while soluble APP is predominantly 105 kDa, does not react with an anti C-terminal antibody, and is 10 kDa shorter than the membrane-bound APP. Amino terminal sequence of the tissue 105 kDa protein indicates that APP begins at residue 18 of the cDNA sequence. These findings imply that i) two forms of APP are detected: membrane-bound and secreted, and ii) APP can be processed in situ.
在阿尔茨海默病中沉积于脑血管壁和老年斑中的淀粉样纤维是一种假定的前体蛋白（APP）经蛋白水解产生的4 kDa片段的聚合形式。使用针对推导的前体的几个片段的抗体，我们能够证明APP存在于老年斑、脑提取物和脑脊液中。膜相关APP被检测为一组105 - 135 kDa的蛋白质，而可溶性APP主要为105 kDa，不与抗C末端抗体反应，比膜结合APP短10 kDa。组织105 kDa蛋白的氨基末端序列表明APP从cDNA序列的第18位残基开始。这些发现意味着：i）检测到两种形式的APP：膜结合型和分泌型；ii）APP可以在原位进行加工处理。
