Role of Complements and Immunoglobulins in Alzheimer’s Disease

Abstract

Our findings show that the value of IgG in serum of Alzheimer’s Disease patients is (17.2059 ± 2.6317) g/l and in controls i.e. (17.6720 ± 3.1457) g/l. Values of IgM in AD patients go down up to 62.5% in comparison to healthy subjects. A sudden change was observed in the levels of IgA of AD patients. It has been put on the value 137.9% high in comparison to healthy subjects. The levels of complement C3 have also value of lower side and go down up to 52.66% in AD patients. The value of levels of complement C4 shows no deflection from the control values. On the basis of regression and multiple correlation analysis, we found that the partial correlation coefficients rGA.M, which has value 0.44815 in AD patients and 0.45555 in controls, do not show any resemblance. The multiple partial correlation rAM.G has value 0.3082 in AD patients and 0.3912 in controls slightly better correlated in comparison to healthy controls. Multiple RA.MG has strongly correlation in comparison to controls. RM.AG is also strongly correlated. Regression coefficients and regression equations are basic foundations of correlation measurements and show a specific character of variation. A relation between all the three multiple correlations has been established in the present work and it is given by the following relation RA.MG > RM.AG > RG.AM.

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Kumar, S. , Mittal, R. , Chaudhary, S. and Jain, D. (2014) Role of Complements and Immunoglobulins in Alzheimer’s Disease. Open Journal of Applied Sciences, 4, 285-298. doi: 10.4236/ojapps.2014.46028.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Sambat, L. (1994) Historical Perspectives. In: Handy, R.C., Turnbull, J.M., Clark, W. and Lan Caster, M.N., Eds., Alzheimer’s Disease. A Hand Book for Care Givers, 2nd Edition, Mosby—Year Book Inc., St. Louis, 51-59.
[2] Reger, B. (2002) Alzheimer’s Disease: A Brief History and Avenues for Current Research. Journal of Young Investigatros, 6, 1-5.
[3] Whaley, N.S. (2002) Senility, Confusion, Debate Fear: Conceptualizing Alzheimer’s Disease and the History of Senile Dementia. Thesis, Drew University, Madism.
[4] Ronald, C.H. and Turnbull, J.M. (1994) Alzheimer’s Disease: An Overview. In: Handy, R.C., Turnbull, J.M., Clark, W. and Lancaster, M.N., Eds., Alzheimer’s Disease. A Hand Book for Care Givers, 2nd Edition, Mosby—Year Book Inc., St. Louis, 1-7.
[5] Cohen, G.D. (2002) Historical Views and Evolution of Concepts. In: Reisberg, B., Ed., Alzheimer’s, Disease, The Free press Macmillan Inc., New York, 29-33.
[6] Rebeca, C.B., Alan, H.L. and Baba Saheb, R.S. (2005) Neuro Degenerative Disease: An Overview of Environmental Risk Factors. Environmental Health Perspectives, 113, 1250-1256.
http://dx.doi.org/10.1289/ehp.7567
[7] Ronald, C.H. and Lorry, B.H. (1994) Factors That Aggravate the Symptoms. In: Handy, R.C., Turnbull, J.M., Clark, W. and Lancaster, M.N., Eds., Alzheimer’s Disease. A Hand Book for Care Givers, 2nd Edition, Mosby—Year Book Inc., St. Louis, 104-116.
[8] Greig, N.H. (2004) New Therapeutic Strategies and Drug Candidates for Neuro-degenrative Disease: P53 and TNF-Alpha Inhibitors, and GLP-1 Recepter Agonists. Annals of the New York Academy of Sciences, 1035, 290-315.
http://dx.doi.org/10.1196/annals.1332.018
[9] Patterson, C., Feightner, J.W., Garcia, A.H., Sing, G.Y., Macknight, C. and Sadovnivk, A.D. (2008) Diagnosis and Treatment of Dementia: 1. Risk Assessment and Primary Prevention of Alzheimer’s Disease. Canadian Medical Association Journal, 178, 548-556.
http://dx.doi.org/10.1503/cmaj.070796
[10] Rosendorff, C., Beeri, M.S. and Silverman, J.M. (2007) Cordiovascular Risk Factors for Alzheimer’s Disease. The American Journal of Geriatric Cardiology, 16, 143-149.
http://dx.doi.org/10.1111/j.1076-7460.2007.06696.x
[11] Solfrizzi, V. (2008) Life Style Related Factors in Predementia and Dementia Syndromes. Expert Review of Neurotherapeutics, 8, 133-158.
http://dx.doi.org/10.1586/14737175.8.1.133
[12] Masters, C.L., Simmus, G., Weinwan, N.A., Multhaup, G., Mc Donald, B.L. and Beyreuther, K. (1985) Amyloid Plaque Core Protein in Alzheimer’s Disease and Down Syndrome. Proceedings of the National Academy of Sciences of the United States of America, 82, 4245-4249.
http://dx.doi.org/10.1073/pnas.82.12.4245
[13] Glenner, G.G. and Wong, C.W. (1984) Alzheimer’s Disease, Initial Report of the Purification and Characterization of a Novel Corebrovascular Amyloid Protein. Biochemical and Biophysical Research Communications, 120, 885-890.
http://dx.doi.org/10.1016/S0006-291X(84)80190-4
[14] Panza, F., Capurso, C., D’Introno, A., Colacicco, A.M., Frisardi, V., Lorusso, M., Santamato, A., Seripa, D., Pilotto, A., Scafato, E., Vendemiate, G., Capurse, A. and Solfrizzi, V. (2009) Alcohol Drinking, Cognitive Functions in Older Age, Predementia and Dementia Syndromes. Journal of Alzheimer’s Disease, 17, 7-31.
[15] Stern, Y.C. (2006) Cognitive Reserve and Alzheimer’s Disease. Alzheimer’s Disease and Associated Disorders, 20, 112-117.
[16] Makinodan, T.C. (1976) Immunobiology of Aging. Journal of the American Geriatrics Society, 24, 249-252.
[17] Burch, P.R.J. (1968) An Inquiry Concerning Growth, Disease and Aging. In: Edinburge, Oliver.
http://dx.doi.org/10.1093/aje/152.1.59
[18] Burnet, F.M. (1970) An Immunological Approach of Aging. The Lancet, 296, 358-360.
http://dx.doi.org/10.1016/S0140-6736(70)92886-2
[19] Kay, M.M.B. and Makinodan, T. (1976) Immunobiology of Aging: Evaluation of Current Status. Clinical Immunology and Immunopathology, 6, 394-413.
[20] Weksler, M.C., Inners, J.D. and Goldstein, G. (1978) Immunological Studies of Aging IV. The Contribution of Thymic Involution to the Immune Deficiencies of Aging Mice and Reversal with Thymopoietin 32-36. Journal of Experimental Medicine, 148, 996-1006.
http://dx.doi.org/10.1084/jem.148.4.996
[21] Weksler, M.E. (1981) The Senescence of the Immune System. Hospital Practice, 16, 53-64.
[22] Wisniewski, H.M. and Terry, R.D. (1973) Morphology of Aging Brain, Human and Animal. Progress in Brain Research, 40, 167-186.
http://dx.doi.org/10.1016/S0079-6123(08)60686-X
[23] Bluestein, H.G. (1978) Neurocytotoxic Antibodies in Serum of Patients with Systemtic Lupus Erythematosus. Proceedings of the National Academy of Sciences of the United States of America, 75, 3965-3969.
http://dx.doi.org/10.1073/pnas.75.8.3965
[24] Heath, R.G. and Krupp, I.M. (1967) Schizophrenia as an Immunologic Disorder. JAMA Psychiatry, 16, 1-9.
http://dx.doi.org/10.1001/archpsyc.1967.01730190003001
[25] Motycka, A. and JezKova, Z. (1975) Auto Antibodies and Brain Ischemia Topography. Casopís Lékaru Ceskych, 114, 1455-1457.
[26] Sakalickova, O., Jezkova, Z. and Jezkova, V. (1962) Immunological Aspects of Psychiatric Gerontology. Review of Czechoslovak Medicine, 8, 264-275.
[27] Pandey, R.S., Gupta, A.K. and Chaturvedi, U.C. (1981) Autoimmune Model of Schizophrenia with Special Reference to Antibrain Antibodies. Biological Psychiatry, 16, 1123-1135.
[28] Husby, G., van de Rijn, I., Zabriska, J.B., Abdin, Z.H. and Williams Jr., R.C. (1976) Antibodies Reacting with Cytoplasm of Subthalamic and Caudate Nuclei Neurons in Chorea and Acute Rheumatic Fever. Journal of Experimental Medicine, 144, 1094-1110.
http://dx.doi.org/10.1084/jem.144.4.1094
[29] Diederrichsen, H. and Pyndt, I.C. (1968) Antibodies against Neurons in a Patient with Systemtic Lupus Erythematosus, Cerebral Palsy and Epilepsy. Brain, 93, 407-412.
http://dx.doi.org/10.1093/brain/93.2.407
[30] Ingram, C.R., Phegan, K.J. and Blumenthal, H.T. (1974) Significance of an Aging-Linked Neuron Binding Gamma Globulin Fraction of Human Sera. Journal of Gerontology, 29, 20-27.
http://dx.doi.org/10.1093/geronj/29.1.20
[31] Lal, H. and Forster, M.J. (1988) Autoimmunity and Age-Associated Cognitive Decline. Neurobiology of Aging, 9, 733-743.
http://dx.doi.org/10.1016/S0197-4580(88)80141-6
[32] Luber-Narod, J. and Rogers, J. (1988) Immune System Associated Antigens Expressed by Cells of the Human Central Nervous System. Neuroscience Letters, 94, 17-22.
http://dx.doi.org/10.1016/0304-3940(88)90263-7
[33] Rogers, J., Luber-Narod, J., Styren, S.D. and Civin, W.H. (1988) Expression of Immune System-Associated Antigens by Cells of the Human Central Nervous System: Relationship to the Pathology of Alzheimer’s Disease. Neurobiology of Aging, 9, 339-349.
http://dx.doi.org/10.1016/S0197-4580(88)80079-4
[34] Styren, S.D., Civin, W.H. and Rogers, J. (1990) Molecular, Cellular and Pathologic Characterization of HLA-DR Immunoreactivity in Normal Elderly and Alzheimer’s Disease Brain. Experimental Neurology, 110, 93-104.
http://dx.doi.org/10.1016/0014-4886(90)90054-V
[35] McGeer, P.L., Akiyama, H., Itagaki, S. and McGeer, E.G. (1990) Immune System Response in Alzheimer’s Disease. Canadian Journal of Neurological Sciences, 16, 516-527.
[36] McGeer, P.L., Itagaki, S., Tago, H. and McGeer, E.G. (1987) Reactive Microglia in Patients with Senile Dementia of the Alzheimer’s Type Are Positive for the Histocompatibility Glycoprotein HLA-DR. Neuroscience Letters, 79, 195-200.
http://dx.doi.org/10.1016/0304-3940(87)90696-3
[37] McGeer, P.L., Itagaki, S., Boyer, B.E. and McGeer, E.G. (1988) Reactive Microglia Are Positive for HLA-DR in the Substantia Nigra of Parkinson’s and Alzheimer’s Disease Brains. Neurology, 20, 1285-1291.
http://dx.doi.org/10.1212/WNL.38.8.1285
[38] McGeer, P.L., Itagaki, S. and McGeer, E.G. (1988) Expression of the Histocompatibility Glycoprotein HLA-DR in Neurological Disease. Acta Neuropathologica, 76, 550-557.
http://dx.doi.org/10.1007/BF00689592
[39] Itagaki, S., McGeer, P.L., Akiyama, H., Zhu, S. and Selkoe, D. (1989) Relationship of Microglia and Astrocytes to Amyloid Deposits of Alzheimer Disease. Journal of Neuroimmunology, 24, 173-182.
http://dx.doi.org/10.1016/0165-5728(89)90115-X
[40] Yamada, T., Akiyama, H. and McGeer, P.L. (1990) Complement-Activated Oligodendroglia: A New Pathologenic Entity Identified by Immunostaining with Antibodies to Human Complement Proteins C3d and C4d. Neuroscience Letters, 112, 161-166.
http://dx.doi.org/10.1016/0304-3940(90)90196-G
[41] Bouras, C., Riederer, B.M., Kovari, E., Hof, P.R. and Giannakopoulos, P. (2005) Humoral Immunity in Brain Aging and Alzheimer’s Disease. Brain Research Reviews, 48, 477-487.
http://dx.doi.org/10.1016/j.brainresrev.2004.09.009
[42] Roitt, I., Brostoff, J. and Male, D. (1985) Immunology. 2nd Edition, C.V. Mosby, St Louis, 459.
[43] Coleman, R.M., Lombard, M.F. and Sicard, R.E. (1992) Fundamental Immunology. Wm. C. Brown Publishers, Dubugue, 459.
[44] Bahananyer, S., Moreau-Dubois, M., Brown, P., Cathala, F. and Gajdvsek, D.C. (1983) Serum Antibodies to Neurofilament Antigens in Patients with Neurological and Other Disease and in Health Controls. Journal of Neuroimmunology, 5, 191-196.
[45] Gaskin, F., Kingsley, B.S. and Fu, S.M. (1987) Autoantibodies to Neurofibrillary Tangles and Brain Tissue in Alzheimer’s Disease. Establishment of Epstein-Barr Virus-Transformed Antibody-Producing Cell Lines. Journal of Experimental Medicine, 165, 245-250.
http://dx.doi.org/10.1084/jem.165.1.245
[46] Terry, R.D., Peck, A., DeTeresa, R., Schechter, R. and Horoupian, D.S. (1981) Some Morphometric Aspects of the Brain in Senile Dementia of the Alzheimer Type. Annals of Neurology, 10, 184-192.
http://dx.doi.org/10.1002/ana.410100209
[47] Rogers, J. and Morrison, J. (1985) Quantitative Morphology and Regional and Laminar Distributions of Senile Plaques in Alzheimer’s Disease. Journal of Neuroscience, 5, 2801-2808.
[48] Rogers, J., Harold, C.W., Styren, S.D. and McGeer, P.L. (1992) Immune-Related Mechanisms of Alzheimer’s Disease Pathogenesis. In: Khachaturian, Z.S. and Blass, J.P., Eds., Alzheimer’s Disease: New Treatment Strategies, Marcel Dekkar, Inc, New York, 147-163.
[49] Gottfries, C.G. (1983) Biochemical Changes in Blood and Cerebrospinal Fluid. In: Reisberg, B., Gottfries, C.G., Blennow, K., Karlsson, I. and Wallin, A., Eds., The Neurochemistry of Alzheimer’s Disease, Free Press, Collier Mac-Millan, London, 122-130.
[50] Cohen, D., Matsuyama, S.S. and Jarvik, L.F. (1976) Immunoglobulin Levels and Intellectual Functioning in the Aged: Short Commun. Journal of the Neurological Sciences, 49, 293-303.
[51] Williams, A., Papadopoulos, N. and Chase, T.N. (1980) Demonstration of CSF Gamma-Globulin Banding Presenile Dementia. Neurology, 30, 882-884.
http://dx.doi.org/10.1212/WNL.30.8.882
[52] Rozemuller, J.M., Eikelenboom, P., Stam, F.C., Befreuther, K. and Masters, C.L. (1989) A4 Protein in Alzheimer’s Disease: Primary and Secondary Cellular Events Extracellular Amyloid Deposition. Journal of Neuropathology & Experimental Neurology, 48, 674-691.
http://dx.doi.org/10.1097/00005072-198911000-00009
[53] Eikelenboom, P. and Stam, F.C. (1982) Immunoglobulins and Complement Factors in Senile Plaques. Acta Neuropathologica, 57, 239-242.
http://dx.doi.org/10.1007/BF00685397
[54] McGeer, P.L., Akiyama, H., Itagaki, S. and McGeer, E.G. (1989) Immune System Response in Alzheimer’s Disease. Canadian Journal of Neurological Sciences, 16, 516-527.
[55] Rogers, J., Schultz, J., Brachova, L., Lue, L.F., Webster, S., Bradt, B., Cooper, N.R. and Moose, D.E. (1992) Complement Activation and β-Amyloid-Mediated Neurotoxicity in Alzheimer’s Disease. Research in Immunology, 143, 624-630.
http://dx.doi.org/10.1016/0923-2494(92)80046-N
[56] McGeer, P.L. and McGeer, E.G. (1992) Complement Proteins and Complement Inhibitors in Alzheimer’s Disease. Research in Immunology, 143, 621-624.
http://dx.doi.org/10.1016/0923-2494(92)80045-M
[57] Eikelenboom, P., Hack, C.E., Kamphorst, W., Vander Walk, P., Vannostrand, W.E. and Rozemuller, J.M. (1993) The Sequence of Neuroimmunological Events in Cerebral Amyloid Plaque Formation in Alzheimer’s Disease. In: Corain, B., Iqbal, K., Nicolini, B.M., Winblad, B., Wisniewski, H. and Zatta, P., Eds., Alzheimer’s Disease: Advances in Clinical and Basic Research, John Wiley & Sons Ltd., Hoboken, 165-170.
[58] Fillits, H., Luine, V.N., Reisberg, B., Amador, R., Mcewen, B. and Zabriskie, J.B. (1985) Studies of the Specificity of Antibrain Antibodies in Alzheimer’s Disease. Neurol.Neurobiol., 18, 307-318.
[59] Fillits, H.M., Kemeny, E., Luine, V., Weksler, M.E. and Zabriskie, J.B. (1987) Antivascular Antibodies in the Sera of Patients with Senile Dementia of the Alzheimer’s Type. Journal of Gerontology, 42, 180-184.
http://dx.doi.org/10.1093/geronj/42.2.180
[60] Singh, V.K. and Fudenberg, H.H. (1986) Detection of Brain Autoantibodies in the Serum of Patients with Alzheimer’s Disease but Not in Down’s Syndrome. Immunology Letters, 12, 277-280.
http://dx.doi.org/10.1016/0165-2478(86)90030-1
[61] Sugiura, M., Yokoi, Y., Maruyama, S., Ishido, T., Tokunaga, Y. and Sasaki, K. (1989) Detection of Anti-Cerebral Autoantibodies in Schizophrenia and Alzheimer’s Disease. Journal of Clinical & Laboratory Immunology, 28, 1-3.
[62] Cohen, D. and Eisdorfer, C. (1980) Serum Immunoglobulins and Cognitive Status in the Elderly: 1. A Population Study. British Journal of Psychiatry, 136, 33-39.
http://dx.doi.org/10.1192/bjp.136.1.33
[63] Eisdorfer, C. and Cohen, D. (1980) Serum Immunoglobulins and Cognitive Status in the Elderly: 2. An Immunological Behavioral Relationship? British Journal of Psychiatry, 136, 40-45.
http://dx.doi.org/10.1192/bjp.136.1.40
[64] Koustsocraki, E. (2008) Immunotherapy in Alzheimer’s Disease. Encephalos, 45, 237-240.
[65] Morgan, B.P., Gasque, P., Singhrao, S. and Piddleshden, S.J. (1997) The Role of Complement in Disorders of the Nervous System. Immunopharmacology, 38, 43-50.
http://dx.doi.org/10.1016/S0162-3109(97)00059-3
[66] Bonifati, D.M. and Kishore, U. (2007) Role of Complement in Neurodegeneration and Neuroinflammation. Molecular Immunology, 44, 999-1010.
http://dx.doi.org/10.1016/j.molimm.2006.03.007
[67] Eikelenboom, P. and Veerhvis, R. (1995) The Role of Complement and Activated Microglia in the Pathogenesis of Alzheimer’s Disease. Neurobiology of Aging, 17, 673-680.
http://dx.doi.org/10.1016/0197-4580(96)00108-X
[68] Watts, H., Kennedy, P.G.E. and Thomas, M. (1981) The Significance of Anti-Neuronal Antibodies in Alzheimer’s Disease. Journal of Neuroimmunology, 1, 107-116.
http://dx.doi.org/10.1016/0165-5728(81)90013-8
[69] Jean, M.S., Marie, C.B. and Gilbert, C. (1994) Comparative Immunohistochemical Characteristics of Human Choroid Plexus in Vascular and Alzheimer’s Dementia. Human Pathology, 125, 1185-1190.
[70] Elovaara, I., Lean, A., Palo, J. and Erkinjuntti, T. (1985) CSF in Alzheimer’s Disease: Studies on Blood Brain Barrier Function and Intrathecal Protein Synthesis. Journal of the Neurological Sciences, 70, 73-80.
http://dx.doi.org/10.1016/0022-510X(85)90189-3
[71] Nerenberg, S.T., Prasad, R. and Rothman, M.E. (1978) Cerebrospinal Fluid IgG, IgA, IgM, IgD and IgE Levels in Central Nervous System Disorders. American Academy of Neurology, 28, 988-990.
http://dx.doi.org/10.1212/WNL.28.10.988
[72] Selkoe, D.J. (1989) Biochemistry of Altered Brain Proteins in Alzheimer’s Disease. Annual Review of Neuroscience, 12, 463-490.
http://dx.doi.org/10.1146/annurev.ne.12.030189.002335
[73] Hampel, H., Müller-Spahn, F., Berger, C., Habert, A., Ackenheil, M. and Hook, C. (1995) Evidence of Blood-Cerebrospinal Fluid-Barrier Impairment in a Subgroup of Patients with Dementia of the Alzheimer Type and Major Depression: A Possible Indicator for Immuno Activation. Dementia and Geriatric Cognitive Disorders, 6, 348-354.
http://dx.doi.org/10.1159/000106969
[74] Bouras, C., Riederer, B.M., Kövari, E., Hof, P.R. and Giannakopoulos, P. (2005) Humoral Immunity in Brain Aging and Alzheimer’s Disease. Brain Research Reviews, 48, 477-487.
http://dx.doi.org/10.1016/j.brainresrev.2004.09.009
[75] Veerhuis, R., Van der Valk, P., Janssen, I.J., Zhan, S.S., Van Nostrand, W.E. and Eikelenboom, P. (1995) Complement Activation in Amyloid Plaques in Alzheimer’s Disease Brains Does not Proceed Further than C3. Virchows Archiv, 426, 603-610.
[76] Kalaria, R.N., Kroon, S.N. and Perry, G. (1993) Serum Proteins and the Blood-Brain Barrier in the Pathogenesis of Alzheimer’s Disease. In: Nicolini, M., Zatta, P.F. and Corain, B., Eds., Alzheimer’s Disease and Altered Disorders, Pergamum Press, Oxford, 281-282.
[77] Kayed, R., Jacksen, G.R., Ester, D.M. and Barrett, A.D. (2011) Alzheimers Disease: Review of Emerging Treatment Role for Intravenous Immunoglobulins. Journal of Central Nervous System Disease, 3, 67-73.
[78] Kumar, S., Kumar, V., Jain, D.C. and Mittal, R. (2013) Immunological Variations in Epileptic Children. Open Journal of Applied Sciences, 3, 71-91.
http://dx.doi.org/10.4236/ojapps.2013.31012
[79] Mancini, G., Carbonara, A.O. and Heremans, J.F. (1965) Immunochemical Quantitation of Antigens by Single Radical Immunodiffusion. Immunochemistry, 2, 235-254.
http://dx.doi.org/10.1016/0019-2791(65)90004-2

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