KP-1 is a marker for extraneuronal neurofibrillary tangles and senile plaques in Alzheimer diseased brains

KP-1 immunostaining with microwave pretreatment in formalin-fixed, paraffin-embedded sections enhanced its immunoreactivity revealing extraneuronal neurofibrillary tangles (NFTs) called ghost tangles, senile plaques (SPs) and perivascular deposits as well as microglial labelling in Alzheimer-diseased brains. KP-1 stained cored and uncored SPs, granules within the SPs, perivascular beta-amyloid protein (beta AP) and star-like beta AP deposits in cortical layer I, which was confirmed in comparison to silver-impregnated structures in the Reusche-stained or Gallyas-Schiff-stained sections. On double immunostaining with KP-1 and ubiquitin, ghost tangles were labelled by KP-1 and intraneuronal NFTs were positive for ubiquitin. A few KP-1-positive granules deposits different from amyloid core were found within the SPs and the outer margin of amyloid cores of SPs were stained by KP-1. KP-1-positive microglia were attached to the ubiquitin-positive intraneuronal NFTs. Microglia were more numerously labelled by CR3/43 than by KP-1, and CR3/43-positive microglia were found to be preferentially attached to SPs. As KP-1 recognizes lysosome-associated antigen CD68, similarities between KP-1 positivity and Reusche-stained structures suggested that lysosomal activity was associated with beta AP deposits and ghost tangles were involved in lysosome-associated processes. It is speculated that lysosomes play a role in the process of ghost tangle formation and in beta AP deposits leading to SP formation.