Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Alzheimer's Disease
Study Details
Study Description
Brief Summary
High lipid peroxidation and altered antioxidant defenses have been frequently reported in Alzheimer's disease patients.
The purpose of this study is to investigate susceptibility to photo-oxidation of isolated erythrocyte membranes, in patients affected by Alzheimer's disease and age- and sex-matched, non demented subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Detailed Description
The study hypothesis is that high lipid peroxidation and decreased antioxidant defenses characterize the natural history of Alzheimer's disease.
It will be evaluated the release of malondialdehyde (MDA) from ex-vivo photo-oxidized erythrocyte ghosts, through a very easy and convenient lab procedure for the preparation of erythrocyte membrane samples.
Isolated and purified red blood cell membranes will be in vitro exposed to oxidative stress by UV-B radiation. The extent of cell membrane damage will be quantified by the fluorometric determination of MDA.
Induction of oxidative stress through ultraviolet rays, unlike that obtained by chemical oxidizing agents, is fully controllable, since it produces effects only during irradiation. Moreover, using isolated erythrocyte membranes allows for a greater specificity in the evaluation of MDA produced, and reduces the amount of blood required for the assay.
A portion of the blood sample (500 µL) will be sent to the laboratory of Lipinutragen (spin-off of CNR- National Research Center Bologna, Italy) where an erythrocyte membrane lipidomic analysis will be performed for the characterization of membrane phospholipids, in order to determinate the different lipid components (saturated fatty acids, monounsaturated and polyunsaturated, trans fatty acids), each one characterized by a different oxidative reactivity.
Recently published papers showed a striking association between urinary excretion of cortisol and the increase of some markers of oxidative damage of DNA and RNA (in humans). This finding provides further support to the idea that chronic psychological stress, who is associated to hypercortisolemia, can lead to an acceleration of the aging process.
The brain is a major target of the effects of glucocorticoids (CCS). The harmful consequences of cortisol on the hippocampus (one of the first brain areas affected by Alzheimer's disease) are well known. Some studies showed inverse correlations between cortisol levels and neuropsychological performance in patients with depression, dementia as well as in people treated chronically with CCS.
Alzheimer's disease is associated with states of hypercortisolism. Nonetheless, so far, its correlation with the level of oxidative stress has not been studied. We will investigate the relationship between 24h excretion of urinary cortisol and the level of malondialdehyde, produced by isolated and purified red blood cell membranes, in vitro exposed to oxidative stress by UV-B radiation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Alzheimer's disease
|
|
| Non demented subjects
|
Outcome Measures
Primary Outcome Measures
- Malondialdehyde assay [At the time of recruitment]
Isolated and purified red blood cell membranes will be in vitro exposed to oxidative stress by UV-B radiation. The extent of cell membrane damage will be quantified by the fluorometric determination of malondialdehyde.
Secondary Outcome Measures
- Relationship between urinary excretion of cortisol and levels of malondialdehyde [At the time of recruitment]
Hyperactivity of the hypothalamic pituitary adrenal axis has been frequently described in Alzheimer's disease. Recently published work reported an association between high secretion of cortisol and oxidative stress. We will investigate the relationship between 24 h excretion of urinary cortisol and the level of malondialdehyde, produced by isolated and purified red blood cell membranes, in vitro exposed to oxidative stress by UV-B radiation.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Outpatients of both sexes diagnosed with Alzheimer's disease according to NINCDS-ADRDA criteria.
-
Age and sex-matched elderly subjects without dementia.
Exclusion Criteria:
-
Recent neoplasia (< 1 year)
-
Vitamin B12 deficiency, positive serology for syphilis, thyroid function abnormalities considered to be significant by the care provider.
-
Use of vitamin or mineral supplements.
-
Diagnosis of malnutrition (based on body mass index and total protein levels)
-
Metabolic syndrome or diabetes.
-
Hormonal replacement therapy.
-
Smoking
-
Chronic inflammatory disease (e.g. rheumatoid arthritis) and any other acute illness.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Policlinico Universitario Campus Bio-Medico | Rome | RM | Italy | 00128 |
Sponsors and Collaborators
- Raffaele Antonelli Incalzi
Investigators
- Principal Investigator: Francesco Maria Serino, M.D. PhD, Doctors in Italy
- Principal Investigator: Chiara Fanali, PhD, University Campus Bio-Medico
- Principal Investigator: Laura Dugo, PhD, University Campus Bio-Medico
- Principal Investigator: Simone Grasso, PhD, University Campus Bio-Medico
- Study Chair: Ettore Bergamini, M.D., University of Pisa
- Principal Investigator: Francesca Ursini, M.D., University Campus Bio-Medico
- Principal Investigator: Fabrizio Vernieri, M.D., University Campus Bio-Medico
- Study Director: Marina Dachà, BS.Pharm, University Campus Bio-Medico
- Principal Investigator: Silvia Bernardini, M.D., University Campus Bio-Medico
- Principal Investigator: Valentina Pasqualetti, PhD, University Campus Bio-Medico
Study Documents (Full-Text)
None provided.More Information
Publications
- Baldeiras I, Santana I, Proença MT, Garrucho MH, Pascoal R, Rodrigues A, Duro D, Oliveira CR. Peripheral oxidative damage in mild cognitive impairment and mild Alzheimer's disease. J Alzheimers Dis. 2008 Sep;15(1):117-28.
- Bermejo P, Gómez-Serranillos P, Santos J, Pastor E, Gil P, Martín-Aragón S. Determination of malonaldehyde in Alzheimer's disease: a comparative study of high-performance liquid chromatography and thiobarbituric acid test. Gerontology. 1997;43(4):218-22.
- Casado A, Encarnación López-Fernández M, Concepción Casado M, de La Torre R. Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res. 2008 Mar;33(3):450-8. Epub 2007 Aug 25.
- Costantini D, Marasco V, Møller AP. A meta-analysis of glucocorticoids as modulators of oxidative stress in vertebrates. J Comp Physiol B. 2011 May;181(4):447-56. doi: 10.1007/s00360-011-0566-2. Epub 2011 Mar 18. Review.
- Davis KL, Davis BM, Greenwald BS, Mohs RC, Mathé AA, Johns CA, Horvath TB. Cortisol and Alzheimer's disease, I: Basal studies. Am J Psychiatry. 1986 Mar;143(3):300-5.
- Galbusera C, Facheris M, Magni F, Galimberti G, Sala G, Tremolada L, Isella V, Guerini FR, Appollonio I, Galli-Kienle M, Ferrarese C. Increased susceptibility to plasma lipid peroxidation in Alzheimer disease patients. Curr Alzheimer Res. 2004 May;1(2):103-9.
- García-Arumí E, Andreu AL, López-Hellín J, Schwartz S. Effect of oxidative stress on lymphocytes from elderly subjects. Clin Sci (Lond). 1998 Apr;94(4):447-52.
- Joergensen A, Broedbaek K, Weimann A, Semba RD, Ferrucci L, Joergensen MB, Poulsen HE. Association between urinary excretion of cortisol and markers of oxidatively damaged DNA and RNA in humans. PLoS One. 2011;6(6):e20795. doi: 10.1371/journal.pone.0020795. Epub 2011 Jun 7.
- Kawamoto EM, Munhoz CD, Glezer I, Bahia VS, Caramelli P, Nitrini R, Gorjão R, Curi R, Scavone C, Marcourakis T. Oxidative state in platelets and erythrocytes in aging and Alzheimer's disease. Neurobiol Aging. 2005 Jun;26(6):857-64.
- Mangialasche F, Polidori MC, Monastero R, Ercolani S, Camarda C, Cecchetti R, Mecocci P. Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment. Ageing Res Rev. 2009 Oct;8(4):285-305. doi: 10.1016/j.arr.2009.04.002. Epub 2009 Apr 17. Review.
- Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997;23(1):134-47. Review.
- Mecocci P. Oxidative stress in mild cognitive impairment and Alzheimer disease: a continuum. J Alzheimers Dis. 2004 Apr;6(2):159-63. Review.
- Onaran I, Yalçin AS, Sultuybek G. Effect of donor age on the susceptibility of erythrocytes and erythrocyte membranes to cumene hydroperoxide-induced oxidative stress. Mech Ageing Dev. 1997 Nov;98(2):127-38.
- Perry G, Nunomura A, Hirai K, Zhu X, Pérez M, Avila J, Castellani RJ, Atwood CS, Aliev G, Sayre LM, Takeda A, Smith MA. Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases? Free Radic Biol Med. 2002 Dec 1;33(11):1475-9. Review.
- Polidori MC, Mecocci P. Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease. J Alzheimers Dis. 2002 Dec;4(6):517-22.
- Serra JA, Domínguez RO, de Lustig ES, Guareschi EM, Famulari AL, Bartolomé EL, Marschoff ER. Parkinson's disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson's, Alzheimer's and vascular dementia patients. J Neural Transm (Vienna). 2001;108(10):1135-48.
- Torres LL, Quaglio NB, de Souza GT, Garcia RT, Dati LM, Moreira WL, Loureiro AP, de Souza-Talarico JN, Smid J, Porto CS, Bottino CM, Nitrini R, Barros SB, Camarini R, Marcourakis T. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 2011;26(1):59-68. doi: 10.3233/JAD-2011-110284.
- ERASE