An immunocytochemical comparison of cytoskeletal proteins in aluminum-induced and Alzheimer-type neurofibrillary tangles

Abstract

Exposure of the central nervous system (CNS) of rabbits to aluminum salts produces a progressive encephalopathy. Examination of CNS structures discloses widespread perikaryal neurofibrillary tangle (NFTs) formation. The aluminum-induced NFTs consist of collections of normal neurofilaments, and differ ultrastructurally and in their solubility characteristics from Alzheimer-type NFTs, the latter being composed of largely insoluble paired helical filaments. The present study compares NFTs found in the rabbit to those of Alzheimer's disease, using monoclonal antibodies (SMI 31, SMI 32) that recognize phosphorylated and non-phosphorylated determinants respectively in normal neurofilaments, and an antiserum raised against purified microtubules. Paraffin-embedded sections were stained by the avidin-biotin immunocytochemical method. Intense staining of aluminum-induced NFTs was found after processing with SMI 31 and SMI 32, while no staining of non-tangled perikarya of control rabbits or of Alzheimer-type NFTs was seen. Antimicrotubule anti-serum gave weak, nonfocal staining in the aluminum-treated and control rabbits, while Alzheimer-type NFTs were stained intensely. These results show that phosphorylated and non-phosphorylated neurofilaments accumulate in aluminum-induced NFTs, thus complementing the previously demonstrated specific slowing of the axonal transport of neurofilaments in aluminum intoxication. Further, they suggest that the presence of microtubular proteins may be necessary for altered neurofilaments to take on a paired helical configuration.