On the survival time of a tangled neuron in the hippocampal CA4 region in parkinsonism dementia complex of Guam

In diseases such as the Parkinson dementia complex of Guam (PDC) or Alzheim er's disease, susceptible neurons develop intracellular tangles (iNFTs) and then die, leaving behind extracellular tangles (eNFTs). We performed count s of healthy neurons, iNFTs, and eNFTs in the hippocampus of Guamanian Cham orros who were neurologically normal or who suffered from PDC. The total of surviving and dead neurons in the CA4 region was remarkably constant from case to case, indicating that eNFTs are not phagocytosed. Since cases of re cent PDC showed only marginal tangle formation in CA4, we concluded that ta ngle development in CA4 commenced close to the onset of the disease. Based on this assumption, as well as the further assumption that the average rate of tangle development and the average lifetime of a tangled neuron do not alter as the disease progresses, we derived equations to determine the aver age lifetime of tangled neurons. The results Varied from 0.13 years for the most rapidly progressing case to 7.98 years for the most slowly developing case. The average for 8 cases was 2.51 years. (C) 1999 Elsevier Science In c. All rights reserved.