The time course of formation of neurofibrillary tangles (NFT) and senile plaques (SP) in Alzheimer's disease (AD) brain is unknown. Above ground nuclear weapons testing in the late 1950s and early 1960s led to significantly increased levels of 14C in the atmosphere and carbon cycle. Because the amyloid beta peptide of SP and paired helical filaments of NFT, once formed, are relatively resistant to degradation, 14C levels observed in SP and NFT should reflect their year of formation. The purpose of this study was to develop a method to determine whether 14C levels could be used to define NFT and SP ages. Using accelerator mass spectrometry to measure bomb-pulse 14C levels, we determined the average age of formation of isolated SP and NFT fractions in bulk brain samples of 6 AD subjects. Although preliminary, the results demonstrate that it is possible to use bomb pulse 14C to determine the average year of formation of NFT and SP in the brain in AD. In addition, the data show that these structures, once formed, have a much slower carbon turnover rate than normal brain and are not in a formation/enzymatic degradation equilibrium.
|Number of pages||8|
|Journal||Neurobiology of Aging|
|State||Published - 2002|
Bibliographical noteFunding Information:
This work was supported by Grants 5P01 AG0 5119 and 5P50 AG0 5144 from the National Institutes of Health and the Abercrombie Foundation. AMS work was completed at Lawrence-Livermore National Laboratory under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory, University of California under contract W7405-Eng-48. The authors thank John Southon for his comments and assistance in making the radiocarbon measurements. We also thank Paula Thomason for editorial assistance, Jane Meara for assistance in manuscript preparation, Cecil Runyons for subject demographic data, and Richard Geissler for assistance with the electron microscopy studies.
- Accelerator mass spectrometry
- Alzheimer's disease
- Neurofibrillary tangles
- Senile plaques
ASJC Scopus subject areas
- Neuroscience (all)
- Developmental Biology
- Clinical Neurology
- Geriatrics and Gerontology