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 ou...
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| Veröffentlicht in: | Neurobiology of aging 2003-09, Vol.24 (5), p.663-673 |
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| creator | Getchell, M.L. Shah, D.S. Buch, S.K. Davis, D.G. Getchell, T.V. |
| description | 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. |
| doi_str_mv | 10.1016/S0197-4580(02)00195-1 |
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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.</description><identifier>ISSN: 0197-4580</identifier><identifier>EISSN: 1558-1497</identifier><identifier>DOI: 10.1016/S0197-4580(02)00195-1</identifier><identifier>PMID: 12885574</identifier><identifier>CODEN: NEAGDO</identifier><language>eng</language><publisher>London: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Alzheimer Disease - complications ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - metabolism ; Biological and medical sciences ; Case-Control Studies ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Female ; Free radicals ; Humans ; Immunohistochemistry - methods ; Male ; Medical sciences ; Mental Status Schedule ; Neurology ; Olfaction Disorders - etiology ; Olfactory Receptor Neurons - metabolism ; Olfactory Receptor Neurons - pathology ; Olfactory threshold ; Oxidative stress ; Peroxynitrite ; Sensory Thresholds - physiology ; Thiolester Hydrolases - metabolism ; Tyrosine - analogs & derivatives ; Tyrosine - metabolism ; Ubiquitin Thiolesterase</subject><ispartof>Neurobiology of aging, 2003-09, Vol.24 (5), p.663-673</ispartof><rights>2002 Elsevier Science Inc.</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-a524519d37220a13631a4ae855d5b4bb598e2d958ccf755cf5dae08e34dcfaf23</citedby><cites>FETCH-LOGICAL-c422t-a524519d37220a13631a4ae855d5b4bb598e2d958ccf755cf5dae08e34dcfaf23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0197458002001951$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14990178$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12885574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Getchell, M.L.</creatorcontrib><creatorcontrib>Shah, D.S.</creatorcontrib><creatorcontrib>Buch, S.K.</creatorcontrib><creatorcontrib>Davis, D.G.</creatorcontrib><creatorcontrib>Getchell, T.V.</creatorcontrib><title>3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer’s disease: implications for impaired odor sensitivity</title><title>Neurobiology of aging</title><addtitle>Neurobiol Aging</addtitle><description>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. 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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.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Alzheimer Disease - complications</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - pathology</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Female</subject><subject>Free radicals</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mental Status Schedule</subject><subject>Neurology</subject><subject>Olfaction Disorders - etiology</subject><subject>Olfactory Receptor Neurons - metabolism</subject><subject>Olfactory Receptor Neurons - pathology</subject><subject>Olfactory threshold</subject><subject>Oxidative stress</subject><subject>Peroxynitrite</subject><subject>Sensory Thresholds - physiology</subject><subject>Thiolester Hydrolases - metabolism</subject><subject>Tyrosine - analogs & derivatives</subject><subject>Tyrosine - metabolism</subject><subject>Ubiquitin Thiolesterase</subject><issn>0197-4580</issn><issn>1558-1497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1uFDEQhS0EIpPAEUDegMKiwb9jdzYoiviTIlgAa8tjlxWj7nZju4OGFVdgyfU4CZ7MiCyzsp_11atyPYSeUPKSErp-9ZnQXnVCanJK2AvSlOzoPbSiUuqOil7dR6v_yBE6LuUbIUQJtX6IjijTWkolVug37z7GmlPd5lTiBDiO4zKlDNbVeB3rFscJpyE0mfIWZ3AwtxueYMlpKjgFPNsaYaoF_4j1Cp8PP68gjpD__vpTsI8FbIGzZjsP0TVyVxSaQXuwMYPHyTdVYCpx3_ARehDsUODx4TxBX9---XLxvrv89O7Dxfll5wRjtbOSCUl7zxVjxFK-5tQKC-1bXm7EZiN7Dcz3UjsXlJQuSG-BaODCu2AD4yfo-d53zun7AqWaMRYHw2AnSEsxikvOCBF3glQTySXhDZR70LVdlgzBzDmONm8NJWYXmrkJzewSMYSZm9AMbXVPDw2WzQj-tuqQUgOeHQBbnB1CtpOL5ZYTfU-o0o17veeg7e06QjbFtWgc-LZpV41P8Y5R_gFOobj9</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>Getchell, M.L.</creator><creator>Shah, D.S.</creator><creator>Buch, S.K.</creator><creator>Davis, D.G.</creator><creator>Getchell, T.V.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20030901</creationdate><title>3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer’s disease: implications for impaired odor sensitivity</title><author>Getchell, M.L. ; Shah, D.S. ; Buch, S.K. ; Davis, D.G. ; Getchell, T.V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-a524519d37220a13631a4ae855d5b4bb598e2d958ccf755cf5dae08e34dcfaf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging</topic><topic>Alzheimer Disease - complications</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - pathology</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, Differentiation, Myelomonocytic - metabolism</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Female</topic><topic>Free radicals</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mental Status Schedule</topic><topic>Neurology</topic><topic>Olfaction Disorders - etiology</topic><topic>Olfactory Receptor Neurons - metabolism</topic><topic>Olfactory Receptor Neurons - pathology</topic><topic>Olfactory threshold</topic><topic>Oxidative stress</topic><topic>Peroxynitrite</topic><topic>Sensory Thresholds - physiology</topic><topic>Thiolester Hydrolases - metabolism</topic><topic>Tyrosine - analogs & derivatives</topic><topic>Tyrosine - metabolism</topic><topic>Ubiquitin Thiolesterase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Getchell, M.L.</creatorcontrib><creatorcontrib>Shah, D.S.</creatorcontrib><creatorcontrib>Buch, S.K.</creatorcontrib><creatorcontrib>Davis, D.G.</creatorcontrib><creatorcontrib>Getchell, T.V.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neurobiology of aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Getchell, M.L.</au><au>Shah, D.S.</au><au>Buch, S.K.</au><au>Davis, D.G.</au><au>Getchell, T.V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer’s disease: implications for impaired odor sensitivity</atitle><jtitle>Neurobiology of aging</jtitle><addtitle>Neurobiol Aging</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>24</volume><issue>5</issue><spage>663</spage><epage>673</epage><pages>663-673</pages><issn>0197-4580</issn><eissn>1558-1497</eissn><coden>NEAGDO</coden><abstract>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.</abstract><cop>London</cop><pub>Elsevier Inc</pub><pmid>12885574</pmid><doi>10.1016/S0197-4580(02)00195-1</doi><tpages>11</tpages></addata></record> |
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| subjects | Aged Aged, 80 and over Aging Alzheimer Disease - complications Alzheimer Disease - metabolism Alzheimer Disease - pathology Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - metabolism Biological and medical sciences Case-Control Studies Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female Free radicals Humans Immunohistochemistry - methods Male Medical sciences Mental Status Schedule Neurology Olfaction Disorders - etiology Olfactory Receptor Neurons - metabolism Olfactory Receptor Neurons - pathology Olfactory threshold Oxidative stress Peroxynitrite Sensory Thresholds - physiology Thiolester Hydrolases - metabolism Tyrosine - analogs & derivatives Tyrosine - metabolism Ubiquitin Thiolesterase |
| title | 3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer’s disease: implications for impaired odor sensitivity |
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