科研之友
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摘要
In Alzheimer's disease (AD), Purkinje neurons in the cerebellum are spared, while, for instance, pyramidal neurons in the hippocampus are neuropathologically affected. Several lines of evidence suggest that the pathogenesis could be induced by the concentration-dependent polymerization of the amyloid beta-peptide (A beta) into extracellular oligomers. The role of intracellular A beta is not fully investigated, but recent data indicate that also this pool could be of importance. Here, we use laser capture microdissection microscopy for isolation of Purkinje neurons from AD cases and controls, and quantify the low levels of intracellular A beta using a novel and highly sensitive ELISA. Similar to Cornu Ammonis 1 pyramidal neurons, the intracellular levels of the most toxic variant, A beta 42, as well as the A beta 42/A beta 40 ratio, were increased in Purkinje neurons from sporadic AD cases as compared to controls. However, the levels of A beta 42 as well as A beta 40 were clearly lower in Purkinje neurons than in pyramidal neurons. Based on the volume of the captured Purkinje neurons, the intraneuronal concentrations of A beta 42 were calculated to be 200 nM in sporadic AD cases and 90 nM in controls. The corresponding concentrations in pyramidal neurons from hippocampus were 3 mu M and 660 nM, respectively. The A beta 40 concentration was not significantly altered in AD cases compared to controls. However, we found ten times higher concentration of A beta 40 in pyramidal neurons (10 mu M) compared to Purkinje neurons (1 mu M). Finally, we suggest that high concentration of intracellular A beta 42 correlates with vulnerability to AD neuropathology.
- 出版日期2010-5
