Study of pathogenesis of Abeta amyloid deposits in Alzheimer's disease

为了阐明阿尔茨海默病中生理多肽，即Aβ淀粉样蛋白(Aβ)的蓄积机制，进行了以下研究：1)转基因小鼠脑和血浆中Aβ40/42的水平(PrPβAPP751NL+I，PrP早老素-1 M146L，通过大规模的多中心研究，发现Abet40/42在APPsw小鼠脑组织中积聚，并且在所有转基因小鼠的脑和血浆中观察到Abeta40/42水平升高。2)正常对照组脑脊液和血浆中Abeta40/42与年龄相关的生理变化。3)通过大规模多中心研究，建立了脑脊液tau和Abeta40/42的临床诊断指标。4)揭示apoE4对痴呆的进展和脑脊液tau浓度的影响。5)AD大鼠脑内Aβ40/42积累量为nmol/g水平，但在对照组的大脑中观察到了任何Abeta的积聚。6)散发性AD和唐氏综合征患者血浆脂蛋白游离Abeta40/42水平升高，提示游离脂蛋白Abeta40/42可能是AD的诊断标志，血浆脂蛋白在Abeta40/42的隔离中起重要作用。

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.