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Induction of Alzheimer Antigens by an Uncoupler of Oxidative Phosphorylation
John P. Blass, MD, PhD;
Andrea C. Baker;
Li-wen Ko, BVM, PhD;
Ronald S. Black, MD
Arch Neurol. 1990;47(8):864-869.
Abstract
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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-µm 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.
Author Affiliations
From the Altschul Laboratory for Dementia Research, Burke Rehabilitation Center, White Plains, NY.
Footnotes
Accepted for publication February 6, 1990.
Presented in part at the Dahlem Conference, Berlin, Germany, December 1987; at the International Conference on Alzheimer's Disease, Las Vegas, Nev, September 1988; at the annual meeting of the Society for Neuroscience, New Orleans, La, November 1987 and Toronto, Canada, November 1988; at the Fondation Ipsen Conference, Toulouse, France, April 1989; and at the International Psychogeriatric Congress, Tokyo, Japan, September 1989.
Reprint requests to the Altschul Laboratory for Dementia Research, Burke Rehabilitation Center, 785 Mamaroneck Ave, White Plains, NY (Dr Blass).
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