EXTRACELLULAR NEUROFIBRILLARY TANGLES REFLECT NEURONAL LOSS AND PROVIDE FURTHER EVIDENCE OF EXTENSIVE PROTEIN CROSS-LINKING IN ALZHEIMER-DISEASE

In this report we quantitatively assess the numbers of intracellular a nd extracellular neurofibrillary tangles (NFT) in the brains of a seri es of individuals with Alzheimer's disease and of controls and correla te these with neuronal loss. Our data indicate that in some cases, NFT are not removed from the brain throughout the disease process. This f inding, together with our previous demonstration of carbonyl-related m odifications in NFT, provides additional evidence that the protein con stituents of NFT are resistant to proteolytic removal, possibly as a r esult of extensive cross-links. Additionally, con-elation between the number of NFT and neuronal loss indicates that there are at least two distinct mechanisms responsible for neuronal death in Alzheimer's dise ase that are directly and indirectly related to the presence of neurof ibrillary pathology.