Alzheimer Disease: Yoshioka K

Mizuno T, Masaaki T, Yoshioka K. · Department of Radiology, Nakamura Memorial Hospital. · Nippon Hoshasen Gijutsu Gakkai Zasshi. · Pubmed #18987416 links to  free full text

Abstract: It has been noted that the manual settings of region of interest (ROI) to the single-photon-emission-computed-tomography (SPECT) slice lacked objectivity when the fixed quantity value of regional cerebral blood flow (rCBF) was measured previously. Therefore, we jointly developed software "Brain ROI" with Daiichi Radioisotope Laboratories, Ltd. (Present name: FUJIFILM RI Pharma Co., Ltd.) The software normalized an individual brain to a standard brain template by using Statistical Parametric Mapping 2 (SPM 2) of the easy Z-score Imaging System ver. 3.0 (eZIS Ver. 3.0), and the ROI template was set to a specific slice. In this study, we evaluated the accuracy of this software with an ROI template that we made of useful size and shape, in some clinical samples. The method of automatic setting of ROI was the objective. However, we felt that we should use the shape of the ROI template without the influence of brain atrophy. Moreover, we should see normalization of the individual brain and confirm the accuracy of normalization. When normalization failed, we should partially correct the ROI or set everything by manual operation for the operator. However, it was thought that this software was useful if the tendency was understood because examples of failure were few.

Tatebayashi Y, Planel E, Chui DH, Sato S, Miyasaka T, Sahara N, Murayama M, Kikuchi N, Yoshioka K, Rivka R, Takashima A. · Laboratory for Alzheimer's Disease, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan. · FASEB J. · Pubmed #16478768 links to  free full text

Abstract: Tauopathies such as Alzheimer disease (AD) probably involve a type of phosphorylation imbalance causing the accumulation of abnormally hyperphosphorylated tau in neurons and/or glias. Investigation of R406W tau mutation may provide insight into such abnormal tau hyperphosphorylation, since this mutation causes AD-like dementia and tauopathy in humans and because it has the unique ability to reduce tau phosphorylation in vitro and in cultured cells. Here we show that R406W mutation primarily disrupts tau phosphorylation at Ser404, a priming phosphorylation site of glycogen synthase kinase-3beta (GSK-3beta), thereby reducing subsequent GSK-3beta-mediated phosphorylation at the PHF-1 site (mostly Ser396). In contrast, c-jun N-terminal kinase (JNK) as activated in the mitotic phase directly hyperphosphorylates R406W tau at the PHF-1 site. This was confirmed by PHF-1 hyperphosphorylation of R406W tau in mitotic cells, its association with cytoplasmic JNK activation, and its inhibition by a JNK inhibitor, SP600125. These data unveil the unknown mechanisms of physiological tau phosphorylation at the PHF-1 site and suggest that cytoplasmic JNK activation may play an important role in the abnormal tau hyperphosphorylation associated with R406W tau mutation and in AD.

Sato S, Tatebayashi Y, Akagi T, Chui DH, Murayama M, Miyasaka T, Planel E, Tanemura K, Sun X, Hashikawa T, Yoshioka K, Ishiguro K, Takashima A. · Laboratory for Alzheimer's Disease, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. · J Biol Chem. · Pubmed #12191990 links to  free full text

Abstract: Neurofibrillary tangles (NFTs) are found in a wide range of neurodegenerative disorders, including Alzheimer's disease. The major component of NFTs is aberrantly hyperphosphorylated microtubule-associated protein tau. Because appropriate in vivo models have been lacking, the role of tau phosphorylation in NFTs formation has remained elusive. Here, we describe a new model in which adenovirus-mediated gene expression of tau, DeltaMEKK, JNK3, and GSK-3beta in COS-7 cells produces most of the pathological phosphorylation epitopes of tau including AT100. Furthermore, this co-expression resulted in the formation of tau aggregates having short fibrils that were detergent-insoluble and Thioflavin-S-reactive. These results suggest that aberrant tau phosphorylation by the combination of these kinases may be involved in "pretangle," oligomeric tau fibril formation in vivo.