Insoluble α-synuclein in Alzheimer's disease without Lewy body formation

被引：11
作者：
Broe, M
Shepherd, CE
Mann, DMA
Milward, EA
Gai, WP
Thiel, E
Halliday, GM [1 ]
机构：
[1] Prince Wales Med Res Inst, Sydney, NSW 2031, Australia
[2] Univ New S Wales, Sydney, NSW 2031, Australia
[3] Univ Manchester, Hope Hosp, Greater Manchester Neurosci Ctr, Clin Neurosci Res Grp, Salford M6 8HD, Lancs, England
[4] Flinders Univ S Australia, Dept Human Physiol, Sch Med, Bedford Pk, SA 5042, Australia
来源：
NEUROTOXICITY RESEARCH | 2005年 / 7卷 / 1-2期
基金：
英国医学研究理事会;
关键词：
Alzheimer's disease; senile plaques; alpha-synuclein; protein solubility;
D O I：
10.1007/BF03033777
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Insoluble alpha-synuclein plays a central role in Lewy body diseases, with considerable controversy as to whether it plays a similar role in Alzheimer's disease (AD). We assessed the tissue location and solubility of cortical alpha-synuclein in AD (without Lewy body formation) compared with controls, using sequential extraction procedures and Western immunoblotting to quantify different alpha-synuclein species in their different solubility states. Controls had no insoluble cortical alpha-synuclein and a ratio of soluble:lipid-associated alpha-synuclein of 1.2 +/- 0.1. Total alpha-synuclein protein was significantly increased in AD and concentrated within the lipid-associated fraction (soluble:lipid ratio 0.9 +/- 0.05, soluble:insoluble 1.5 +/- 0.1, lipid:insoluble 1.7 +/- 0.1) which proved difficult to localize in paraffin-embedded tissue. Tissues prepared without lipid extraction revealed alpha-synuclein-immunoreactivity in the amorphous components of mature cored AD plaques. This lipid-association of alpha-synuclein in mature AD plaques links this protein with other lipid changes thought to be important in disease pathogenesis.
引用
收藏
页码：69 / 76
页数：8
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