Alzheimer's soluble amyloid β is a normal component of human urine

FEBS Letters

Frangione, Blas¹  Governale, Samuel¹  Wisniewski, Thomas³  Beavis, Ronald⁴  Ghiso, Jorge¹  Chuba, Joseph¹  Matsubara, Etsuro²  Calero, Miguel¹ 

[1] Department of Pathology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA;Department of Neurology, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi 371, Gunma, Japan;Department of Neurology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA;Department of Pharmacology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA

关键词: Alzheimer's disease;    Down's syndrome;    Proteinuria;    Saβ;   

DOI  :  10.1016/S0014-5793(97)00400-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Soluble Aβ (Saβ) is normally present at a low concentration in human plasma and cerebrospinal fluid. Although the factors involved in the regulation of Saβ plasma levels are still unknown, we have explored its excretion in the urine as one of the possible homeostatic mechanisms. The presence of Saβ in the urine was investigated via immunoprecipitation experiments with anti-Aβ antibodies followed by detection and identification by immunoblot, MALDI mass spectrometry and sequence analysis. Soluble Aβ (4.3 kDa) immunoreactivity was present in the urine of normal donors, Down's syndrome individuals as well as in patients with renal disorders exhibiting glomerular or mixed proteinuria. Edman degradation of the immunoprecipitated material yielded the intact Aβ N-terminus and mass spectra analysis indicated the existence of a major component at m/z 4327, corresponding to the molecular mass of Aβ1-40. Semiquantitative data obtained from the immunoprecipitation experiments indicate that under normal conditions the daily excretion of intact Saβ in the urine represents less than 1% of the circulating pool.

【 授权许可】

Unknown