Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation
J. P. Blass, A. C. Baker, L. Ko and R. S. Black
Altschul Laboratory for Dementia Research, Burke Rehabilitation Center, White Plains, NY.
Since previous studies have suggested that the coupling of oxidation to
phosphorylation is impaired in Alzheimer brain and fibroblasts, the effects
of carbonyl cyanide m-chlorophenylhydrazone, a hydrazone known to uncouple
mitochondrial oxidative phosphorylation, were tested on the development of
immunoreactivity with antibodies to "Alzheimer antigens" in cultured
fibroblasts from cognitively intact subjects. The fibroblasts were exposed
for 10 to 14 days to a medium (DMd) modeled on media that favor neuronal
differentiation in fetal brain cultures. The addition of a 10-microns
concentration of carbonyl cyanide m-chlorophenylhydrazone to the DMd
culture medium increased by more than 10-fold the proportion of cells
reacting immunocytochemically with antibodies to paired helical filaments
and by 157-fold the proportion of cells reacting with the Alz-50 monoclonal
antibody. These observations suggest that the oxidative abnormalities
previously described in tissues from patients with Alzheimer's disease may
contribute to the accumulation of abnormal cytoskeletal materials in this
disorder.
