In the Indiana kindred of Gerstmann-Sträussler-Scheinker disease, neurofibrillary tangles (NFT) with paired helical filaments (PHF) are numerous, widespread and consistently present in the cerebral cortex and several subcortical nuclei. Such tangles share antigenic determinants with those of Alzheimer disease; in fact, they are recognized by Alz50, anti-PHF and anti-ubiquitin antibodies. Thus, NFT with structural and immunocytochemical similarities are present in two distinct forms of amyloidosis of the central nervous system, i.e. the Indiana kindred of Gerstmann-Sträussler-Scheinker disease and Alzheimer disease.