Abeta42-carboxy-terminal-like immunoreactivity is associated with intracellular neurofibrillary tangles and pick...

Co-occurrence of neurofibrillary tangles (NFTs) and beta-amyloid (Abeta)-containing plaques is the pathological hallmark of Alzheimer's disease (AD). Much research has been carried out to elucidate the possible interactions of these two characteristic lesions. Here we show by immunohistochemistry that an Abeta42-carboxy-terminal-like epitope (tAbeta42) is associated with NFTs at an early, intraneuronal stage. The NFTs immunoreactive for tAbeta42 were also positive for tau2. tAbeta42 NFTs occurred even in cases without plaques or any other form of extracellular Abeta deposits. NFTs were tAbeta42 immunoreactive under all tangle forming conditions studied: AD, the parkinsonism dementia complex of Guam, progressive supranuclear palsy, and elderly controls. In Pick disease, which is another "tauopathy" Pick bodies and ballooned neurons were found to be immunoreactive for tAbeta42. Appearance of an epitope of Abeta in neurons at such an early stage of tangle formation and in Pick bodies may indicate a direct connection of Abeta42 and cytoskeletal disarrangement, although cross-reactivity with other epitopes cannot be ruled out.