Antibodies to neurofibrillary tangles of Alzheimer's disease raised from human and animal neurofilament fractions.

Antibodies reacting with neurofibrillary tangles (NFT) of Alzheimer's disease were consistently obtained using neurofilament (NF) fractions as antigen. NF fractions were obtained from normal human spinal roots or guinea pig peripheral nerves and used to immunize BALB/c mice. Mice receiving a total dose of 300 to 600 micrograms of protein developed antibodies that were indistinguishable with immunostaining of tissues and of polypeptides separated on sodium dodecyl sulfate-polyacrylamide electrophoresis gels. These antibodies reacted with NFT from cases of Alzheimer's disease and with NFT induced with aluminum, as well as with structures rich in NF such as central and peripheral axons and cerebellar basket fibers. When used to immunostain polypeptides separated by sodium dodecyl sulfate-polyacrylamide electrophoresis, all antisera recognized the three NF subunits. Absorption of the antisera with 5 micrograms/ml of purified human NF proteins blocked immunostaining of Alzheimer's NFT. It is concluded that human and animal NF fractions are excellent antigens to produce antibodies that consistently react with NFT of Alzheimer's disease. The present findings further support existing evidence that the paired helical filaments of Alzheimer's disease share antigenic determinants with normal NF.