Heterogeneity in Alzheimer's disease: evidence from cellular radiosensitivity and complementation of this phenotype

Radiosensitivity was studied in a series of Alzheimer's disease (AD) patients and normal controls by examining clonogenic survival and radiation-induced chromosome aberrations in lymphoblastoid cell lines. D0 values based on colony survival for AD and normals following exposure to gamma-rays were 0.86 +/- 0.04 and 1.14 +/- 0.03 Gy respectively. However, 2 of the AD cell lines had D0 values in the normal range. This increased radiosensitivity in AD cells was confirmed by an increased number of gamma-ray-induced chromosome aberrations in these cells. Cell fusion was employed to investigate the presence of different complementation groups for the radiosensitive phenotype in AD using frequency of radiation-induced chromosome aberrations as a means of distinguishing different groups. Four complementation groups were found among 5 AD cell lines. These findings provide additional experimental evidence in support of heterogeneity in AD.