3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer's disease: implications for impaired odor sensitivity.
Olfactory sensory function is impaired in patients with the diagnosis of probable Alzheimer's disease (AD) compared to elderly controls, and the olfactory epithelium (OE) of AD patients exhibits several pathological changes characteristic of the AD brain. To confirm that the populations from whom our postmortem tissues are obtained exhibit similar decrements in sensory function, threshold testing was performed; probable AD patients had significantly higher olfactory thresholds than controls. To determine if oxidative stress contributes to decreased olfactory function in AD, we localized 3-nitrotyrosine (3-NT) immunoreactivity in OE obtained postmortem from patients with neuropathologically confirmed AD and age-matched controls with brains free of significant neurodegenerative pathology. In AD patients, immunoreactivity was localized in olfactory receptor neurons (ORNs), including dendritic knobs where ion channels that participate in sensory transduction are located, suggesting a direct mechanism for olfactory impairment. In controls, immunoreactivity occurred in blood vessel endothelium, suggesting age-related vascular dysfunction. Immunohistochemistry for CD68, a macrophage scavenger receptor, demonstrated activated macrophages, a source of free radicals contributing to 3-NT formation, in the OE of AD patients but not controls. These results demonstrate increased oxidative stress and modification of ORN proteins that may contribute directly to olfactory impairment in AD patients.
Getchell
M L
ML
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. mgetch@pop.uky.edu
Shah
D S
DS
Buch
S K
SK
Davis
D G
DG
Getchell
T V
TV
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D000857:Olfaction Disorders / Q000209:etiology*; D018034:Olfactory Receptor Neurons / Q000378:metabolism* / Q000473:pathology; D012684:Sensory Thresholds / Q000502:physiology; D013869:Thiolester Hydrolases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D013869:Thiolester Hydrolases; D014443:Tyrosine; D043222:Ubiquitin Thiolesterase; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C002744:3-nitrotyrosine