Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process.

Intracellular amyloid ß peptide (Aß) accumulation has drawn attention in relation to the pathophysiology of Alzheimer's disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aß is one of the possible mechanisms by which intracellular Aß deposits form. Given the relevance of Aß inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aß in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-ß-cyclodextrin or treatment with trypsin diminished the internalization of oAß, suggesting that the oAß uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aß (oAß). oAß-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAß is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAß42 enters cells.

[A case of hemichorea caused by right internal carotid artery stenosis].

This is a case of a 71 years old man. Hemichorea appeared in the left half of his body in the middle of November, 2014. Minute hyperintense areas in the white matter near the posterior horn of the right lateral ventricle and in the right parasagittal frontal cortex was shown in MRI diffusion weighted image. Severe stenosis was seen in the right internal carotid artery, and reduction in cerebral blood flow of the right cerebral hemisphere including the basal ganglia was shown in single photon emission computed tomography (SPECT). After having carotid endarterectomy of the right internal carotid artery in January, 2015, hemichorea disappeared, and the cerebral blood flow of the right cerebral hemisphere improved. It is known that hemichorea is caused by the infarction of the basal ganglia. In recent years, some hemichorea cases are reported around East Asia caused by internal carotid artery stenosis with reduction in cerebral blood flow.