The distribution of karyopherin β proteins in Alzheimer's disease

Abstract

Electron microscopic studies of Alzheimer's disease (AD) revealed an intimate relationship between paired helical filaments and nuclear pores, structures with a key role in bidirectional nucleocytoplasmic transport. This association led us to explore potential abnormalities in transport that may contribute to tangle formation and other protein aggregates in neurodegenerative disease. Previously, we found that antibodies to several nucleoporins highlighted neuronal nuclear contour and irregularity in AD. Immunohistochemical study of nuclear transport factor 2 (NTF2) revealed increased cytoplasmic label in neurons and RanBP2/nup358 antibody labeled tangle‐bearing neurons and Hirano bodies. In the present study, we examined the distribution of karyopherinβ (Kapβ) in AD hippocampus. This group of proteins is variously involved in docking to the nuclear pore complex and importing ribosomal and other proteins into the nucleus. Using antibodies to Kapβ1, β2, and β3, we labeled sections in 3 AD and 3 control cases. Kapβ1 and Kapβ3 displayed finely granular cytoplasmic immunopositivity, the latter with extensive dendritic label. Kapβ2 antibody revealed striking large cytoplasmic granules in many hippocampal neurons, more prominent in AD than controls. Kapβ2 also was present in some tangle‐bearing cells. Further characterization of transport proteins and their potential role in AD is warranted.