Non-Alzheimer neurofibrillary tangles show beta-amyloid-like immunoreactivity

As well as being a neuropathological hallmark of Alzheimer's disease (AD), neurofibrillary tangles (NFT) are present in the brain in a number of other neurodegenerative conditions. beta-Amyloid (beta/A4) plaque formation is a central event in AD, although recent reports indicate that beta/A4, and its precursor protein (beta APP), are also associated with AD NFT. Using an antibody to a beta APP epitope overlapping the beta/A4 region, we demonstrate that immunoreactivity is found in extracellular NFT in Niemann-Pick disease, Hallervorden-Spatz disease, progressive supranuclear palsy and subacute sclerosing panencephalitis. These NFT were not labelled with a beta/A4 antibody which recognizes plaque beta/A4 in AD, which supports the proposal that beta/A4 can exist in different conformations. Our results also imply a common mechanism of NFT development in different neurodegenerative conditions, including those not normally associated with substantial beta/A4 deposition or beta APP involvement.