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

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.