title: Detection of tau proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay.
abstract: Alzheimer's disease is a progressive degenerative dementia characterized by the abundant presence of neurofibrillary tangles in neurons. This study was designed to test whether the microtubule-associated protein tau, a major component of neurofibrillary tangles, could be detected in CSF. Additionally, we investigated whether CSF tau levels were abnormal in Alzheimer's disease as compared with a large group of control patients. We developed a sensitive sandwich enzyme-linked immunosorbent assay using AT120, a monoclonal antibody directed to human tau, as a capturing antibody. With this technique, the detection limit for tau was less than 5 pg/ml of CSF. Using AT8, which recognizes abnormally phosphorylated serines 199-202 in tau, the detection limit was below 20 pg/ml of CSF. However, with AT8, we found no immunoreactivity in CSF, suggesting that only a small fraction of CSF tau contains the abnormally phosphorylated AT8 epitope. Our results indicate that CSF tau levels are significantly increased in Alzheimer's disease. Also, CSF tau levels in a large group of patients with a diversity of neurological diseases showed overlap with CSF tau levels in Alzheimer's disease.
authors.affiliation: Laboratory of Neurobiology, Born-Bunge Foundation, University of Antwerp, Wilrijk, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Vandermeeren
authors.forename: M
authors.initials: M
authors.lastname: Mercken
authors.forename: E
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: J
authors.initials: J
authors.lastname: Six
authors.forename: A
authors.initials: A
authors.lastname: van de Voorde
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Cras
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D012016:Reference Values; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D000911:Antibodies, Monoclonal; D016875:tau Proteins