Timothy C Durazzo1, Niklas Mattsson2, Michael W Weiner3, Magdalena Korecka4, John Q Trojanowski4, Leslie M Shaw4. 1. Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. Electronic address: timothy.durazzo@ucsf.edu. 2. Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 3. Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; Departments of Psychiatry, Medicine, and Neurology, University of California, San Francisco Psychiatry, University of California, San Francisco, CA, USA. 4. Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Diseases Research, Perelman School of Medicine, University of Pennsylvania, USA.
Abstract
BACKGROUND: Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS. METHODS: Elders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. RESULTS: Smokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years. CONCLUSIONS: This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.
BACKGROUND: Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS. METHODS: Elders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. RESULTS: Smokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years. CONCLUSIONS: This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.
Authors: Raymond C S Seet; Chung-Yung J Lee; Wai Mun Loke; Shan Hong Huang; Huiwen Huang; Woan Foon Looi; Eng Soh Chew; Amy M L Quek; Erle C H Lim; Barry Halliwell Journal: Free Radic Biol Med Date: 2011-03-17 Impact factor: 7.376
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Christopher M Clark; Paul S Aisen; Ronald C Petersen; Kaj Blennow; Holly Soares; Adam Simon; Piotr Lewczuk; Robert Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2009-04 Impact factor: 10.422
Authors: S Mitchell Harman; Lynn Liang; Panayiotis D Tsitouras; Frank Gucciardo; Christopher B Heward; Peter D Reaven; Wei Ping; Alaa Ahmed; Richard G Cutler Journal: Free Radic Biol Med Date: 2003-11-15 Impact factor: 7.376
Authors: Timothy C Durazzo; Anderson Mon; David Pennington; Christoph Abé; Stefan Gazdzinski; Dieter J Meyerhoff Journal: Addict Biol Date: 2012-09-03 Impact factor: 4.280
Authors: Michael W Weiner; Dallas P Veitch; Paul S Aisen; Laurel A Beckett; Nigel J Cairns; Robert C Green; Danielle Harvey; Clifford R Jack; William Jagust; John C Morris; Ronald C Petersen; Andrew J Saykin; Leslie M Shaw; Arthur W Toga; John Q Trojanowski Journal: Alzheimers Dement Date: 2017-03-22 Impact factor: 21.566
Authors: Timothy C Durazzo; Magdalena Korecka; John Q Trojanowski; Michael W Weiner; Ruth O' Hara; John W Ashford; Leslie M Shaw Journal: J Alzheimers Dis Date: 2016-07-25 Impact factor: 4.472
Authors: Ju-Hee Kang; Magdalena Korecka; Michal J Figurski; Jon B Toledo; Kaj Blennow; Henrik Zetterberg; Teresa Waligorska; Magdalena Brylska; Leona Fields; Nirali Shah; Holly Soares; Robert A Dean; Hugo Vanderstichele; Ronald C Petersen; Paul S Aisen; Andrew J Saykin; Michael W Weiner; John Q Trojanowski; Leslie M Shaw Journal: Alzheimers Dement Date: 2015-07 Impact factor: 21.566