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The τ Protein in Human Cerebrospinal Fluid in Alzheimer's Disease Consists of Proteolytically Derived Fragments
Authors:Gail V. W. Johnson,Peter Seubert,Teresa M. Cox,Ruth Motter,&dagger  Jason P. Brown, &dagger   Douglas Galasko
Affiliation:Department of Psychiatry, University of Alabama at Birmingham, Birmingham, Alabama;; Athena Neurosciences, South San Francisco, California;and; University of California, San Diego and Veterans Affairs Medical Center, San Diego, California, U.S.A.
Abstract: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 τ fragments were also detected. No intact τ 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 τ with alkaline phosphatase did not alter the electrophoretic properties of the fragments. These studies clearly demonstrate that CSF τ is truncated rather than intact.
Keywords:Cerebrospinal fluid    τ    Alzheimer's disease    Stroke
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