The τ protein in human cerebrospinal fluid in Alzheimer's disease consists of proteolytically derived fragments

Abstract

Previous studies have shown that the levels of the microtubule- associated protein τ in the CSF of patients with Alzheimer's disease (AD) are elevated compared with age-matched controls. In spite of these findings, the nature of τ in CSF has not been well documented. In the present study, τ was immunoprecipitated from CSF of patients with AD or acute stroke, as well as normal elderly controls, followed by immunoblot analysis. In all cases, CSF τ consisted primarily of a band migrating at 26-28 kDa. In AD and stroke patients, several smaller r fragments were also detected. No intact ττ was detected in any of the CSF samples examined. Further immunoprecipitation studies showed that the majority of the τ fragments contained the amino terminus of the molecule. Treatment of CSF r with alkaline phosphatase did not alter the electrophoretic properties of the fragments. These studies clearly demonstrate that CSF τ is truncated rather than intact.