Aβ42-carboxy-terminaI-like immunoreactivity is associated with intracellular neurofibrillary tangles and pick bodies

Co-occurrence of neurofibrillary tangles (NFTs) and beta-amyloid (A beta)-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 A beta 42-carboxy-terminal-like epitope (tA beta 42) is associated With NFTs at an early, intraneuronal stage. The NFTs immunoreactive for tA beta 42 were also positive for tau2. tA beta 42 NFTs occurred even in cases without plaques or any other form of extracellular A beta deposits. NFTs were tA beta 42 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 tA beta 42. Appearance of an epitope of A beta in neurons at such an early stage of tangle formation and in Pick bodies may indicate a direct connection of A beta 42 and cytoskeletal disarrangement, although cross-reactivity with other epitopes cannot be ruled out. (C) 2000 Academic Press.