DETECTION OF TAU PROTEINS IN NORMAL AND ALZHEIMERS-DISEASE CEREBROSPINAL-FLUID WITH A SENSITIVE SANDWICH ENZYME-LINKED-IMMUNOSORBENT-ASSAY

Alzheimer's disease is a progressive degenerative dementia characteriz ed by the abundant presence of neurofibrillary tangles in neurons. Thi s study was designed to test whether the microtubule-associated protei n tau, a major component of neurofibrillary tangles, could be detected in CSF. Additionally, we investigated whether CSF tau levels were abn ormal in Alzheimer's disease as compared with a large group of control patients. We developed a sensitive sandwich enzyme-linked immunosorbe nt 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 2 0 pg/ml of CSF. However, with AT8, we found no immunoreactivity in CSF , suggesting that only a small fraction of CSF tau contains the abnorm ally phosphorylated AT8 epitope. Our results indicate that CSF tau lev els are significantly increased in Alzheimer's disease. Also, CSF tau levels in a large group of patients with a diversity of neurological d iseases showed overlap with CSF tau levels in Alzheimer's disease.