Goux Warren J., Liu Bingcam, Shumburo Abdurahman M., Parikh Samir, Sparkman Dennis R.
Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, TX 75083-0688, USA.
J Alzheimers Dis. 2001 Oct;3(5):455-466. doi: 10.3233/jad-2001-3504.
Protease resistant paired helical filaments (prcPHF) can be isolated from the brains of Alzheimer's diseased patients. A second type of PHF, A68 PHF, may be extracted in soluble form from brain homogenate and induced to form filaments in vitro. Here we use a variety of analytical techniques to assess the protein, carbohydrate and fatty acid composition of prcPHF and A68 PHF. High-field ^1H NMR of both PHF preparations display similar fatty acid and carbohydrate proton resonances, consistent with the presence of a structurally similar glycolipid. Carbohydrate analysis showed that both preparations contained greater than 82% less than 12% C16:1 was significantly lower in A68 PHF than in prcPHF, both preparations contained otherwise similar fatty acid profiles with the most abundant lipid component being oleic acid (C18:1, 29.3 +/- 9.0%) followed by palmitic (C16:0, 28.5 +/- 5.6%) 17.6 +/- 7.5%) preparations revealed a profile reasonably consistent with that previously determined for PHF-tau but significantly higher in glycine and lower in lysine than would be predicted from the cDNA sequence. On a weight per cent basis, protein accounted for about 51% A68 PHF samples but only about 10% Carbohydrate and fatty acid accounted for about 39% A68 PHF samples but 74% preparations showed strong correlations between the total amount of tau protein and fatty acid. These results suggest that a glycolipid component forms an integral part of the PHF structure.
抗蛋白酶双螺旋丝（prcPHF）可从阿尔茨海默病患者的大脑中分离出来。第二种类型的双螺旋丝，即A68 PHF，可以以可溶形式从脑匀浆中提取出来，并在体外诱导形成丝状物。在这里，我们使用各种分析技术来评估prcPHF和A68 PHF的蛋白质、碳水化合物和脂肪酸组成。两种双螺旋丝制剂的高场^1H NMR显示出相似的脂肪酸和碳水化合物质子共振，这与存在结构相似的糖脂一致。碳水化合物分析表明，两种制剂含有的小于12%的碳水化合物含量均超过82%，A68 PHF中的C16:1显著低于prcPHF，两种制剂的脂肪酸谱在其他方面相似，最丰富的脂质成分是油酸（C18:1，29.3±9.0%），其次是棕榈酸（C16:0，28.5±5.6%），17.6±7.5%的制剂显示出与先前确定的PHF-tau相当一致的谱，但甘氨酸含量显著高于预期，赖氨酸含量低于cDNA序列预测值。以重量百分比计算，蛋白质在A68 PHF样品中约占51%，但在prcPHF中仅约占10%。碳水化合物和脂肪酸在A68 PHF样品中约占39%，但在prcPHF中占74%。两种制剂中tau蛋白总量与脂肪酸之间存在强相关性。这些结果表明，糖脂成分是双螺旋丝结构的一个组成部分。
