Project/Area Number |
10832003
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
老化(加齢)
|
Research Institution | Gunma University |
Principal Investigator |
SHOJI Mikio School of Medicine, Gunma University Lecturer, 医学部, 講師 (60171021)
|
Co-Investigator(Kenkyū-buntansha) |
HARIGAYA Yasuo School of Medicine, Gunma University Lecturer, 医学部, 講師 (90165035)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | Alzheimer's disease / Amyloid / Abeta 42 / Aβ40 / リポ蛋白結合型 / リポ蛋白非結合型 / 血液Aβ / Aβ / 脳Aβ / 脳脊髄液Aβ |
Research Abstract |
To clarify the accumulation mechanism of physiological peptide, i.e., Abeta amyloid protein (Abeta) in Alzheimer's disease, studies described below were conducted. 1) The levels of Abeta 40/42 of the brain and plasma in transgenic mice (PrP betaAPP751 NL+I, PrP presenilin-1 M146L, PrP presenilin-1 C410Y and APPsw mice) were evaluated showing nmol/g levels Abeta 40/42 were accumulated in the APPsw brain and fmol and pmol level increase of Abeta 40/42 were observed in the brain and plasma in all transgenic mice line. 2) The age-related physiological alteration of Abeta 40/42 in CSF and plasma were observed in normal control subjects. 3) The clinical usefulness of measurement of CSF tau and Abeta 40/42 is established for a diagnosic marker for AD by large scale multicenter study. 4) The effect of apoE4 on advance of dementia and CSF tau concentrations were revealed. 5) The amounts of Abeta 40/42 accumulation in the AD brain were nmol/g levels, but any Abeta accumulation was observed in control brains. Abeta 40 was detected in normal human urine. 6) Plasma lipoprotein unbinding Abeta 40/42 was increased in sporadic AD and Down syndrome patients showing the levels of lipoprotein free Abeta40/42 as the possible diagnostic marker for AD and the important role of plasma lipoprotein for sequestration Abeta40/42.
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