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Analysis of the relationship between Amyloid β protein and cholesterol in Alzheimer's disease.

Research Project

Project/Area Number 15590891
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNational University Corporation Tottori University

Principal Investigator

URAKAMI Katsuya  Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (30213507)

Co-Investigator(Kenkyū-buntansha) TANIGUCHI Miyako  Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (50335527)
NAKASHIMA Kenji  Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (70144673)
WAKUTANI Yousuke  Tottori University, Faculty of Medicine, Research Associate, 医学部, 助手 (10322215)
OHNO Kousaku  Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (70112109)
NINOMIYA Haruaki  Tottori University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (80212124)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsAlzheimer's disease(AD) / Amyloid R protein precursor(APP) / Amyloid β protein(Aβ) / Cholesterol / LDL / secretase / α-セレクターゼ / アミロイドβタンパク (Aβ) / リノール酸 / アミロイドβ蛋白(Aβ) / ニーマン・ピック病C型 / アルミニウム
Research Abstract

Alzheimer's disease (AD) is one of the most frequent neurodegenerative disorders in elder people. Familial AD is known to be caused by mutations in the amyloid β protein precursor (APP), Presenilin 1 or 2, though these causes of AD are relatively uncommon. But those genetic risk factors account for less than 2% of all AD causes, remaining are sporadic AD.
Amyloid β protein (Aβ) is one of the abnormally accumulated proteins in AD's brain. Aβ fibril formation and deposition long have been linked to the neuropathogenesis of AD. And abnormal processing of APP and increase in Aβ may play a major role in the pathogenesis of the hereditary forms and also that of sporadic AD.
We investigate the relationship between APP, Aβ and cholesterol to find the evidence that cholesterol may play a role in the cleavage of APP. We made APP-overexpressed CHO cells and npc1 defected CHO (nCHO) cells by transfect the wild type, Swedish and Tottori (D678N) type mutated APP. Npc1 is defected in Niemann-Pick disease type C, which has lack in intracellular transport and maintenance of homeostasis of cholesterol. We analyzed intracellular quantity, synthesis and esterification of cholesterol, but excess APP had no effects directly. Then we determined intracellular APP levels and production Aβ in different intracellular cholesterol background using both cells with extracellular stimulation of Aluminum, LDL and oxidative stress.
Despite no relationship APP, Aβ and Aluminum, more sensitive against Aluminum in nCHO cells compared normal cells. Exposure of excess LDL induced the cleavage of APP by β-secretase in nCHO cells, which indicated Aβ production. Intracellular APP levels on the oxidative stress were decreased in CHO cells but not affected in nCHO. Fewer lipids in nCHO of membrane in nCHO may prevent the oxidative attack against cell membrane.
The disruption of cholesterol homeostasis might accelerate and strengthen the risks in AD.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (23 results)

All 2005 2004 Other

All Journal Article (16 results) Book (1 results) Publications (6 results)

  • [Journal Article] Cerebrospinal fluid phosphorylated tau protein at serin199 is a useful diagnostic biomarker in Alzheimer's disease and mild cognitive impairment.2005

    • Author(s)
      Urakami K, et al.
    • Journal Title

      Recent Progress In Alzheimer's And Parkinson's Diseases

      Pages: 177-182

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Studies on diagnostic markers Alzheimer's disease.2005

    • Author(s)
      Urakami k, et al.
    • Journal Title

      Psychogeriatrics 5・3

      Pages: 99-102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] アルツハイマー病の危険因子と予防の可能性 年齢、性別、教育歴2005

    • Author(s)
      浦上克哉
    • Journal Title

      モダンフィジシャン 25・9

      Pages: 1056-1057

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] アルツハイマー型痴呆のスクリーニング2005

    • Author(s)
      浦上克哉
    • Journal Title

      CLINICIAN 52・543

      Pages: 24-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Cerebrospinal fluid phosphorylated tau protein at serin199 is a useful diagnostic biomarker in Alzheimer's disease and mild cognitive impairment.2005

    • Author(s)
      Urakami K, Arai H, Itoh N, Ishiguro K, Oono H, Taniguchi M, Wada-Isoe K, Wakutani Y, Kuzuhara S, Sasaki H, Nakashima K, Imahori K.
    • Journal Title

      Recent Progress In Alzheimer's And Parkinson's Diseases

      Pages: 177-182

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Studies on diagnostic markers Alzheimer's disease.2005

    • Author(s)
      Urakami K, Taniguchi M, Inoue M, Wada-Isoe K, Wakutani Y, Nakashima K.
    • Journal Title

      Psychogeriatrics 5(3)

      Pages: 99-102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The risk factor and possibility of the prevention of Alzheimer's disease.-Age, se, and carrier of education- (Japanese)2005

    • Author(s)
      Urakami K
    • Journal Title

      Modem Physician 25(9)

      Pages: 1056-1057

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Screening of Alzheimer's disease.(Jananese)2005

    • Author(s)
      Urakami K
    • Journal Title

      CLINICIAN 52(543)

      Pages: 24-28

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cerebrospinal fluid phosphorylated tau protein at serin199 is a useful diagnostic biomarker it Alzheimer's disease and mild cognitive impairment.2005

    • Author(s)
      Urakami K et al.
    • Journal Title

      Recent Progress In Alzheimer's And Parkinson's Diseases

      Pages: 177-182

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Studies on diagnostic markers Alzheimer's disease.2005

    • Author(s)
      Urakami K et al.
    • Journal Title

      Psychogeriatrics 5・3

      Pages: 99-102

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 他疾患との鑑別・除外診断2004

    • Author(s)
      浦上克哉
    • Journal Title

      DDL magazine

      Pages: 16-19

    • Related Report
      2004 Annual Research Report
  • [Journal Article] アルツハイマー病の遺伝的危険因子2004

    • Author(s)
      浦上克哉, 谷口美也子, 山形薫, 和田健二, 涌谷陽介, 中島健二
    • Journal Title

      Medical Science Digest 30・6

      Pages: 20-25

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic Analysis of Familial Alzheimer's Disease in a Japanese Population2004

    • Author(s)
      Wakutani Y, Adachi Y, Wada-Isoe K, Yamagata K, Urakami K, Nakashima K
    • Journal Title

      Moiecular Neurobiology of Alzheimer Disease and Related Disorders

      Pages: 157-163

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Soluble Aβ homeostasis in AD and DS : impairment of antiamyloidogenic protection by lipoproteins2004

    • Author(s)
      Matsubara E, Sekijima Y, Tokuda T, Urakami K, et al.
    • Journal Title

      Neurobiology of Aging 25

      Pages: 833-841

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel presenilin 1 mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis2004

    • Author(s)
      Hattori H, Sakuma K, Wakutani Y, Wada K, Shimoda M, Urakami K, Kowa H, Nakashima K
    • Journal Title

      Neuroscience Letters 368

      Pages: 319-322

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 痴呆治療の基礎「中核症状に対する薬物療法」2004

    • Author(s)
      浦上克哉
    • Journal Title

      Progress in Medicine 24・10

      Pages: 2433-2436

    • Related Report
      2004 Annual Research Report
  • [Book] 新しい診断と治療のABC別冊2004

    • Author(s)
      浦上克哉, 谷口美也子
    • Total Pages
      223
    • Publisher
      最新医学社
    • Related Report
      2004 Annual Research Report
  • [Publications] 浦上克哉, 谷口美也子: "アルツハイマー病に対するその他の治療の試みの現況"老年精神医学雑誌. 14・5. 567-569 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe Y, Shimizu Y, Urakami K, Matsushima E, Nakashima K: "Vertical ophthalmoplegia in a demented patient with striato pallidodentate calcification"Psychiatry Clin.Neurosci.. 57・4. 447-450 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inoue M, Suyama A, Kato T, Urakami K, Nakashima K, Meshitsuka S: "Development of computerized Kana Pick out test for the neuropsychological examination"Comput.Meth.Programs Biomed.. 70. 271-276 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wakutani Y, Watanabe K, Adachi Y, Isoe-Wada K, Urakami K, et al.: "Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease"J.Neurol.Neurosurg.Psychiatr.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wakutani Y, Kowa H, Kusumi M, Nakaso K, Yasui K, Wada-Isoe K, Urakami K, et al.: "The regulatory region polymorphisms of the MTHFR gene are not associated with Alzheimer's disease"Dement.Geriatr.Cogn.Disord.. 17・3. 147-150 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 浦上克哉: "医学大辞典"医学書院. 3090 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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