Ultrastructural localization of heme oxygenase-1 to the neurofibrillary pathology of Alzheimer disease

Evidence for the important role of oxidation and free radicals in aging and Alzheimer disease (AD), the leading cause of senile dementia, is increasing. Indeed, we recently demonstrated that the antioxidant heme oxygenase-1 (HO-1) enzyme is localized to the neurofibrillary pathology of AD. HO-1 is found intimately associated with the neurofibrillary tangles (NFT), senile plaque neurites, and neuropil threads within the Alzheimer brain, whereas control brains show only sporadic lesion-related immunoreactivity in age-matched tissue and negligible background in tissue from young controls. HO-1 is an inducible microsomal enzyme that oxidatively cleaves heme, a pro-oxidant, to produce biliverdin and carbon monoxide. Biliverdin is converted by biliverdin reductase to bilirubin, a potent antioxidant, whereas within the brain, carbon monoxide is suggested to act as a neurotransmitter. This latter aspect led to the suggestion that increased HO-1 activity might cause carbon monoxide-induced excitotoxicity and lead to neuronal degeneration. The present article reports the electron microscopic localization of HO-1.