IMMUNOHISTOCHEMICAL STAGING OF NEUROFIBRILLARY DEGENERATION IN ALZHEIMERS-DISEASE

Antibodies to different phosphorylated and non-phosphorylated tau epit opes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughou t the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immuno reactivity and retention of other tau epitopes. Dispersed extracellula r tangles (Type 3) were characterized by the presence of epitopes asso ciated with the microtubule binding region and the COOH-terminus. Thes e three types of tangles, found in situ in hippocampus, could be creat ed experimentally by proteolytic treatment of brain sections. These fi ndings suggest that three stages of neurofibrillary degeneration can b e understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phospho rylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.