NEUROFIBRILLARY TANGLES IN NIEMANN-PICK DISEASE TYPE-C

Post-mortem neuropathological examination of five cases of Niemann-Pic k disease type C revealed neurofibrillary tangles in many parts of the brain. Tangles were a consistent finding in the hippocampus, hypothal amus, substantia innominata, midbrain pons and medulla. Other regions of the brain in which tangles were present included neocortex, basal g anglia, thalamus, cerebellar cortex in one case, and dentate nucleus i n another. The tangles were argyrophilic, fluoresced under ultraviolet light when stained with thioflavin S, and reacted strongly with antib ody to tau protein. Some of the tangles could be immunostained for ubi quitin. Electron microscopy, performed in one of the cases, showed the tangles to consist of paired helical filaments ultrastructurally iden tical to those of Alzheimer's disease. The distribution of the tangles in the central nervous system as a whole and also within many individ ual neurons corresponded fairly closely with that of the abnormal stor age material. Both the tangles and the storage material extended into, and distended the proximal parts of many dendrites and axons. No A4/b eta protein, either in the form of plaques or in the walls of blood ve ssels, was detected in any of the cases. Our findings suggest that neu rofibrillary tangles are a common feature of Neimann-Pick disease type C and that their formation may be a reaction to the abnormal storage material.