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1996 Fiscal Year Final Research Report Summary

An Attempt to Identify Amyloid Precursor Protein Processing Pathway Involving Lysosomal System by Vesicle Specific Protein

Research Project

Project/Area Number 07671080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionSAPPORO MEDICAL UNIVERSITY

Principal Investigator

TAKAHATA Naohiko  SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE DEPT.OF NEUROPSYCHIATRY PROFESSOR, 医学部, 教授 (20000987)

Co-Investigator(Kenkyū-buntansha) FUJII Mitsuru  SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE DEPT.OF NEUROPSYCHIATRY ASSISTANT, 医学部, 講師 (80199299)
FUKATSU Ryo  SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE DEPT.OF NEUROPSYCHIATRY ASSOCIATE, 医学部, 助教授 (10113614)
Project Period (FY) 1995 – 1996
Keywordsamyloid precursor protein / amyloid beta protein / lysosomal pathway / proteolytic processing / vesicular transport / clathrin / beta-COP chloroquine / cultured myocyte
Research Abstract

The lysosomal pathway has been suggested as the site of formation for amyloidogenic amyloid precursor protein (APP) fragment and amyloid beta protein (Abeta). Lysosomes are, however, meeting places in which several streams of intracellular traffic converge. We describe here an attempt to identify APP processing pathway involving lysosomal system by vesicle specific protein
1. Antibodies raised against transport vesicle specific proteins : There are clathrin-coated vesicle, and non-clathrin coated vesicle, designated as coatmer protein-coated vesicle of transport vesicles. We were successful in raising antibodies against synthetic peptides homologous to amino acid sequence of clathrin, and beta-COP.
2. Proteolytic processing of APP in cultured human myocyte treated with/without concanamycin A (Con A) : Con A inhibits selectively endocytosis from cell surface to intracsllular compartments via clathrin-coated vesicles.
1) Histopathological studies of cultured myocytes : Vacuoles appeared ben … More eath the plasma membrane in the cultured myocytes 12 hours after Con A treatment, and increase in number until up to 24 hours.
2) Immunopathological studies of APP and Abeta localization : Con A induced vacuoles were labeled with anti-APP,and anti-Abeta antibodies. A number of these vacuoles were also atained with clathrin antibody. Interestingly, beta-COP antibody labeled unique dot-like structures in the cytoplasm without Con A treatment. Cultured myocytes treated with Con A,vacuoles were labeled with beta-COP antibody. But no immunoreactivities were observed with anti-ERGIC 53, specific for endoplasmic reticulum, and with anti-garactosyltransferase, specific protein to Golgi apparatus.
3. Biochemical studies on proteolytic processing of APP : Metabolic labeling of cultured myocytes were performed of cultured myocytes treated with/without Con A.APP and Abeta in the cell lysates were immunoprecipitated with specific antibodies against APP,and Abeta. Subsequently, eluates were separated on electrophoresis, and then subjected to autoragiography. 4 kDa Abeta fragment was detected in cell lysate without Con A treatment, and this 4 kDa Abeta fragment increased their intensity after Con A treatment.
Our data indicate that non-clathrin coated vesicles to acidic compartments, lysosomes, may play an important role in the generation of amyloidogenic fragments and Abeta, in addition to clathrin-coated vesicles. Less

  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tsuzuki K et al: "Amyloid β protein and transthyretin,sequestraing protein colocalize in normal human kidney" Neuroscience Letters. 222. 163-166 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuzuki K et al: "Snake coiled fibers in rat soleusmuscle in chloroquine induced myopathy share immunohistochemical characteristicswith amyloid depositions in Alzheimer's disease brain" International Journal of Experimental Pathology. 78. 1-8 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 深津 亮 他: "アミロイド前駆体蛋白の処理過程とアルツハイマー病" 老年精神医学雑誌. 10. 1091-1104 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida T et al: "Amyloid precursor protein, Aβ and amyloid-associated proteins involved chloroquine retinopathy in rats-immunopathological studies" Brain Research. 764. 283-288 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aizawa Y et al: "Amino-terminus truncated apolipoprotein E is the major species in amyloid deposits in Alzheimer's disease-affected brains : a possible role for apolipoprotein E in Alzheimer's disease" Brain Research. 768. 208-214 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi Y et al: "Evidence for presenilin-1 involvement in amylod angiopathy in the Alzheimer's disease-affected brain" Brain Research. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 深津 亮 他: "KEY WORD 1997-'98精神" 先端医学社, 2 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukatsu R et al: "Membranous lipodistrophy (Nasu-Hakola disease) with Alzheimer's senile change." In Nicolini M,Zatta PF and Corain B (eds). Pergamon Press, New York ; Advances in the Biosciences, Alzheimer's disease and related disorders.87. 33-34 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Potentially amyloidogenic fragment of 50 kDa and intracellular processing of amyloid precursor protein in cell cultured under leupeptin." Brain Research. 659. 213-220 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Immunohistochemical evidence for amyloid beta in rat soleus muscles in chloroquine-induced myopathy." Neuroscience Letters. 182. 151-154 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Amyloidogenic fragment of amyloid precursor protein in cell cultured under leupeptin." In Israel H,Abraham F,and Yoshida M,Alzheimer's and Parkinson's Disease : Recent Developments. 119-125 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takamaru Y et al: "Identification and role of non-beta component of senile plaque amyloid in Alzheimer's disease." In Israel H,Abraham Fand Yoshida M,Alzheimer's and Parkinson's Disease : Recent Developments. 149-155 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takamaru Y et al: "Apolipoprotein E in senile plaque." Ronenseishinigaku zasshi. 6. 1129-1137 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Co-localization of amyloid associated proteins with amyloid beta in rat soleus muscle in chloroquine-induced myopathy : a possible model for amyloid beta formation in Alzheimer's disease." Brain Research. 699. 260-265 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Amyloid beta protein in rat soleus muscle in chloroquine induced myopathy using end-specific antibodies for Abeta40 and Abeta42 -Immunohistochemical evidence for amyloid beta protein-." Neuroscience Letters. 202. 77-80 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Chloroquine-induced myopathy as a possible model for Alzheimer's disease." Ronenkichihoukenkyukaishi. 9. 1-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukatsu R et al: "Biological characteristics of amyloid precursor protein and Alzheimer's disease." Japanese Journal of Clinical Pathology. 44. 213-224 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukatsu R et al: "Aging brains and the dementias." Hokkaido Journal of Medical Sciences. 71. 297-301 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukatsu R et al: "Recent advances in Alzheimer's disease research -amyloid precursor protein trafficking, processing, and mutations in Alzheimer's disease linked genes-." Hokkaido Journal of Medical Sciences. 72. 3-11 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukatsu R et al: "Processing of amyloid precursor protein and the pathogenesis of Alzheimer's disease." Ronenseishinigaku zasshi. 10. 1091-1104 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Snake coiled fibers in rat soleus muscle in chloroquine induced myopathy share immunohistochemical characteristics with amyloid depositions in Alzheimer's disease brain." International Journal of Experimental Pathology. 78. 1-8 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki K et al: "Amyloid beta protein and transthyretin, sequestraing protein colocalize in normal human kidney." Neuroscience Letters. 222. 163-166 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida T et al: "Amyloid precursor protein, Abeta and amyloid-associated proteins involved chloroquine retinopathy in rats -immunopathological studies." Brain Research. 764. 283-288 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aizawa Y et al: "Amino-terminus truncated apolipoprotein E is the major species in amyloid deposits in Alzheimer's disease-affected brains : a possible role for apolipoprotein E in Alzheimer's disease." Brain Research. 768. 208-214 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi Y et al: "Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain." Brain Research. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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