Therapeutic Effects of Curcumin on Alzheimer’s Disease


As the number of patients with Alzheimer’s disease (AD) continues to rise throughout the twenty- first century, scientists are increasingly looking for remedies, although the cause and pathology of the disease remain uncertain. Among treatments for AD, there is a renewed interest in curcumin as a potential medication. Studies of the substance have found a large amount of consumption associated benefits, including anti-inflammatory and antioxidant effects. Its wide healing properties make it increasingly interesting to scientists, with potential uses in the treatment of cancers, arthritis, various cardiovascular diseases, and neurodegenerative diseases. More recently, curcumin has been shown to have multipotent effects against various symptoms of AD. Among other things, curcumin has been able to ameliorate toxicity of beta-amyloid species, a key part of AD nuerodegeneration, in vivo and in vitro, and has been able to inhibit multiple parts along suspected AD pathology. The goal of this review is to summarize the research done on curcumin with respect to its applicability as a treatment for AD and AD related pathology.

Share and Cite:

Yao, E. and Xue, L. (2014) Therapeutic Effects of Curcumin on Alzheimer’s Disease. Advances in Alzheimer's Disease, 3, 145-159. doi: 10.4236/aad.2014.34014.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Alzheimer’s Association (2014) Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 10, e47-e92.
[2] Hebert, L.E., Beckett, L.A., Scherr, P.A. and Evans, D.A. (2001) Annual Incidence of Alzheimer Disease in the United States Projected to the Years 2000 through 2050. Alzheimer Disease and Associated Disorders, 15, 169-173.
[3] Alzheimer, A., Stelzmann, R.A., Schnitzlein, H.N. and Murtagh, F.R. (1995) An English Translation of Alzheimer’s 1907 Paper, Uber eine eigenartige Erkankung der Hirnrinde. Clinical Anatomy, 8, 429-431.
[4] Lorenzo, A. and Yankner, B.A. (1994) Beta-Amyloid Neurotoxicity Requires Fibril Formation and Is Inhibited by Congo Red. Proceedings of the National Academy of Sciences of the United States of America, 91, 12243-12247.
[5] Zetterberg, H., Blennow, K. and Hanse, E. (2010) Amyloid Beta and APP as Biomarkers for Alzheimer’s Disease. Experimental Gerontolog, 45, 23-29.
[6] Shankar, G.M., Li, S., Mehta, T.H., Garcia-Munoz, A., Shepardson, N.E., Smith, I., et al. (2008) Amyloid-Beta Protein Dimers Isolated Directly from Alzheimer’s Brains Impair Synaptic Plasticity and Memory. Nature Medicine, 14, 837- 842. Http://Dx.Doi.Org/10.1038/Nm1782
[7] Broersen, K., Rousseau, F. and Schymkowitz, J. (2010) The Culprit behind Amyloid Beta Peptide Related Neurotoxicity in Alzheimer’s Disease: Oligomer Size or Conformation? Alzheimer’s Research & Therapy, 2, 12.
[8] McLean, C.A., Cherny, R.A., Fraser, F.W., Fuller, S.J., Smith, M.J., Beyreuther, K., Bush, A.I. and Masters, D.L. (1999) Soluble Pool of Abeta Amyloid as a Determinant of Severity of Neurodegeneration in Alzheimer’s Disease. Annals of Neurology, 46, 860-866.<860::AID-ANA8>3.0.CO;2-M
[9] Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S., et al. (2002) Naturally Secreted Oligomers of Amyloid Beta Protein Potently Inhibit Hippocampal Long-Term Potentiation in Vivo. Nature, 416, 535-539.
[10] Yankner, B.A. (1996) Mechanisms of Neuronal Degeneration in Alzheimer’s Disease. Neuron, 16, 921-932.
[11] Goel, A., Kunnumakkara, A.B. and Aggarwal, B.B. (2008) Curcumin as “Curecumin”: From Kitchen to Clinic. Biochemical Pharmacology, 75, 787-809.
[12] Mohandas, E., Rajmohan, V. and Raghunath, B. (2009) Neurobiology of Alzheimer’s Disease. Indian Journal of Psychiatry, 51, 55-61.
[13] Chintamaneni, M. and Bhaskar, M. (2012) Biomarkers in Alzheimer’s Disease: A Review. ISRN Pharmacology, 2012, Article ID: 984786.
[14] Maccioni, R.B., Farias, G., Morales, I. and Navarrete, L. (2010) The Revitalized Tau Hypothesis on Alzheimer’s Disease. Archives of Medical Research, 41, 226-231.
[15] Metzler, M., Pfeiffer, E., Schulz, S.I. and Dempe, J.S. (2013) Curcumin Uptake and Metabolism. BioFactors, 39, 14- 20.
[16] Indira Priyadarsini, K. (2013) Chemical and Structural Features Influencing the Biological Activity of Curcumin. Current Pharmaceutical Design, 19, 2093-2100.
[17] Aggarwal, B.B., Kumar, A. and Bharti, A.C. (2003) Anticancer Potential of Curcumin: Preclinical and Clinical Studies. Anticancer Research, 23, 363-398.
[18] Menon, V.P. and Sudheer, A.R. (2007) Antioxidant and Anti-Inflammatory Properties of Curcumin. In: Aggarwal, B.B., Surh, Y.-J. and Shishodia, S., Eds., The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer US, New York, 105-125.
[19] Xu, X.B., Chen, B. and Liu, W.Y. (2014) Curcumin Inhibits the Invasion of Thyroid Cancer Cells via Down-Regulation of PI3K/Akt Signaling Pathway. Gene, 546, 226-232.
[20] Terlikowska, K., Witkowska, A. and Terlikowski, S. (2013) Curcumin in Chemoprevention of Breast Cancer. Postepy Higieny i Medycyny Doswiadczalnej (Online), 68, 571-578.
[21] Pyun, C.W., Kim, J.H., Han, K.H., Hong, G.E. and Lee, C.H. (2014) In Vivo Protective Effects of Dietary Curcumin and Capsaicin against Alcohol-Induced Oxidative Stress. BioFactors, in Press.
[22] Zeng, Y., Liu, J., Huang, Z., Pan, X. and Zhang, L. (2014) Effect of Curcumin on Antioxidant Function in the Mice with Acute Alcoholic Liver Injury. Journal of Hygiene Research, 43, 282-285.
[23] Ganguli, M., Chandra, V., Kamboh, M.I., Johnston, J.M., Dodge, H.H., Thelma, B.K., et al. (2000) Apolipoprotein E Polymorphism and Alzheimer Disease: The Indo-US Cross-National Dementia Study. Archives of Neurology, 57, 824- 830.
[24] Ng, T.P., Chiam, P.C., Lee, T., Chua, H.C., Lim, L. and Kua, E.H. (2006) Curry Consumption and Cognitive Function in the Elderly. American Journal of Epidemiology, 164, 898-906.
[25] Ak, T. and Gülçin, Ï. (2008) Antioxidant and Radical Scavenging Properties of Curcumin. Chemico-Biological Interactions, 174, 27-37.
[26] Begum, A.N., Jones, M.R., Lim, G.P., Morihara, T., Kim, P., Heath, D.D., et al. (2008) Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer’s Disease. Journal of Pharmacology and Experimental Therapeutics, 326, 196-208.
[27] Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., et al. (2005) Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo. Journal of Biological Chemistry, 280, 5892-5901.
[28] Mishra, S. and Palanivelu, K. (2008) The Effect of Curcumin (Turmeric) on Alzheimer’s Disease: An Overview. Annals of Indian Academy of Neurology, 11, 13-19.
[29] Lin, L.C. and Tsai, T.H. (2011) Curcumin and Its Nano-Formulation: The Kinetics of Tissue Distribution and Blood- Brain Barrier Penetration. International Journal of Pharmaceutics, 416, 331-338.
[30] Jiang, J., Wang, W., Sun, Y.J., Hu, M., Li, F. and Zhu, D.Y. (2007) Neuroprotective Effect of Curcumin on Focal Cerebral Ischemic Rats by Preventing Blood-Brain Barrier Damage. European Journal of Pharmacology, 561, 54-62.
[31] Wang, X., Kim, J.R., Lee, S.B., Kim, Y.J., Jung, M.Y., Kwon, H.W. and Ahn, Y.J. (2014) Effects of Curcuminoids Identified in Rhizomes of Curcuma longa on BACE-1 Inhibitory and Behavioral Activity and Lifespan of Alzheimer’s Disease Drosophila Models. BMC Complementary and Alternative Medicine, 14, 88.
[32] Deshpande, A., Mina, E., Glabe, C. and Busciglio, J. (2006) Different Conformations of Amyloid β Induce Neurotoxicity by Distinct Mechanisms in Human Cortical Neurons. The Journal of Neuroscience, 26, 6011-6018.
[33] Busciglio, J., Lorenzo, A., Yeh, J. and Yankner, B.A. (1995) Beta-Amyloid Fibrils Induce Tau Phosphorylation and Loss of Microtubule Binding. Neuron, 14, 879-888.
[34] Li, S., Jin, M., Koeglsperger, T., Shepardson, N.E., Shankar, G.M. and Selkoe, D.J. (2011) Soluble Aβ Oligomers Inhibit Long-Term Potentiation through a Mechanism Involving Excessive Activation of Extrasynaptic NR2B-Containing NMDA Receptors. The Journal of Neuroscience, 31, 6627-6638.
[35] Naslund, J., et al. (2000) Correlation between Elevated Levels of Amyloid Beta-Peptide in the Brain and Cognitive Decline. JAMA, 83, 1571-1577.
[36] Bush, A. and Tanzi, R. (2008) Therapeutics for Alzheimer’s Disease Based on the Metal Hypothesis. Neurotherapeutics, 5, 421-432.
[37] Lambracht-Washington, D. and Rosenberg, R.N. (2013) Anti-Amyloid-Beta to Tau-Based Immunization: Developments in Immunotherapy for Alzheimer’s Disease. ImmunoTargets and Therapy, 2, 105-114.
[38] Anastasio, T.J. (2014) Computational Identification of Potential Multitarget Treatments for Ameliorating the Adverse Effects of Amyloid-β on Synaptic Plasticity. Frontiers in Pharmacology, 5, 85.
[39] Alzheimer’s Association (2008) Experimental Alzheimer Drugs Targeting Beta-Amyloid and the “Amyloid Hypothesis”.
[40] Lim, G.P., Chu, T., Yang, F., Beech, W., Frautschy, S.A. and Cole, G.M. (2001) The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse. The Journal of Neuroscience, 21, 8370-8377.
[41] Garcia-Alloza, M., Borrelli, L.A., Rozkalne, A., Hyman, B.T. and Bacskai, B.J. (2007) Curcumin Labels Amyloid Pathology in Vivo, Disrupts Existing Plaques, and Partially Restores Distorted Neurites in an Alzheimer Mouse Model. Journal of Neurochemistry, 102, 1095-1104.
[42] Caesar, I., Jonson, M., Nilsson, K.P.R., Thor, S. and Hammarström, P. (2012) Curcumin Promotes A-Beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila. PLoS ONE, 7, e31424.
[43] Zhao, L.N., Chiu, S.W., Benoit, J., Chew, L.Y. and Mu, Y. (2012) The Effect of Curcumin on the Stability of Aβ Dimers. The Journal of Physical Chemistry B, 116, 7428-7435.
[44] Reinke, A.A. and Gestwicki, J.E. (2007) Structure-Activity Relationships of Amyloid Beta-Aggregation Inhibitors Based on Curcumin: Influence of Linker Length and Flexibility. Chemical Biology & Drug Design, 70, 206-215.
[45] Masuda, Y., Fukuchi, M., Yatagawa, T., Tada, M., Takeda, K., Irie, K., et al. (2011) Solid-State NMR Analysis of Interaction Sites of Curcumin and 42-Residue Amyloid β-Protein Fibrils. Bioorganic & Medicinal Chemistry, 19, 5967- 5974.
[46] Fiala, M., Lin, J., Ringman, J., Kermani-Arab, V., Tsao, G., Patel, A., et al. (2005) Ineffective Phagocytosis of Amyloid-β by Macrophages of Alzheimer’s Disease Patients. Journal of Alzheimer’s Disease, 7, 221-232.
[47] Weiner, H.L. and Selkoe, D.J. (2002) Inflammation and Therapeutic Vaccination in CNS Diseases. Nature, 420, 879- 884.
[48] Bard, F., et al. (2000) Peripherally Administered Antibodies against Amyloid β-Peptide Enter the Central Nervous System and Reduce Pathology in a Mouse Model of Alzheimer Disease. Nature Medicine, 6, 916-919.
[49] Zhang, L., et al. (2006) Curcuminoids Enhance Amyloid-β Uptake by Macrophages of Alzheimer’s Disease Patients. Journal of Alzheimer’s Disease, 10, 1-7.
[50] Puglielli, L., Tanzi, R.E. and Kovacs, D.M. (2003) Alzheimer’s Disease: The Cholesterol Connection. Nature Neuroscience, 6, 345-351.
[51] Regitz, C. and Wenzel, U. (2014) Amyloid-Beta (Aβ1-42)-Induced Paralysis in Caenorhabditis elegans Is Reduced by Restricted Cholesterol Supply. Neuroscience Letters, 576, 93-96.
[52] Wong, B.X., Hung, Y.H., Bush, A.I. and Duce, J.A. (2014) Metals and Cholesterol: Two Sides of the Same Coin in Alzheimer’s Disease Pathology. Frontiers in Aging Neuroscience, 6, 91.
[53] Popp, J., Lewczuk, P., Kölsch, H., Meichsner, S., Maier, W., Kornhuber, J., et al. (2012) Cholesterol Metabolism Is Associated with Soluble Amyloid Precursor Protein Production in Alzheimer’s Disease. Journal of Neurochemistry, 123, 310-316.
[54] Wood, W.G., Li, L., Müller, W.E. and Eckert, G.P. (2014) Cholesterol as a Causative Factor in Alzheimer’s Disease: A Debatable Hypothesis. Journal of Neurochemistry, 129, 559-572.
[55] Gamba, P., Testa, G., Sottero, B., Gargiulo, S., Poli, G. and Leonarduzzi, G. (2012) The Link between Altered Cholesterol Metabolism and Alzheimer’s Disease. Annals of the New York Academy of Sciences, 1259, 54-64.
[56] Heverin, M., Bogdanovic, N., Lütjohann, D., Bayer, T., Pikuleva, I., Bretillon, L., et al. (2004) Changes in the Levels of Cerebral and Extracerebral Sterols in the Brain of Patients with Alzheimer’s Disease. Journal of Lipid Research, 45, 186-193.
[57] Igbavboa, U., Pidcock, J.M., Johnson, L.N., Malo, T.M., Studniski, A.E., Yu, S., et al. (2003) Cholesterol Distribution in the Golgi Complex of DITNC1 Astrocytes Is Differentially Altered by Fresh and Aged Amyloid β-Peptide-(1-42). Journal of Biological Chemistry, 278, 17150-17157.
[58] Maulik, M., Westaway, D., Jhamandas, J.H. and Kar, S. (2013) Role of Cholesterol in APP Metabolism and Its Significance in Alzheimer’s Disease Pathogenesis. Molecular Neurobiology, 47, 37-63.
[59] Beel, A.J., Sakakura, M., Barrett, P.J. and Sanders, C.R. (2010) Direct Binding of Cholesterol to the Amyloid Precursor Protein: An Important Interaction in Lipid-Alzheimer’s Disease Relationships? Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1801, 975-982.
[60] Bodovitz, S. and Klein, W.L. (1996) Cholesterol Modulates-Secretase Cleavage of Amyloid Precursor Protein. Journal of Biological Chemistry, 271, 4436-4440.
[61] Soni, K.B. and Kuttan, R. (1992) Effect of Oral Curcumin Administration on Serum Peroxides and Cholesterol Levels in Human Volunteers. Indian Journal of Physiology and Pharmacology, 36, 273-273.
[62] Ringman, J.M., Frautschy, S.A., Cole, G.M., Masterman, D.L. and Cummings, J.L. (2005) A Potential Role of the Curry Spice Curcumin in Alzheimer’s Disease. Current Alzheimer Research, 2, 131-136.
[63] Sahebkar, A. (2014) A Systematic Review and Meta-Analysis of Randomized Controlled Trials Investigating the Effects of Curcumin on Blood Lipid Levels. Clinical Nutrition, 33, 406-414.
[64] White, A.R., Reyes, R., Mercer, J.F., Camakaris, J., Zheng, H., Bush, A.I., et al. (1999) Copper Levels Are Increased in the Cerebral Cortex and Liver of APP and APLP2 Knockout Mice. Brain Research, 842, 439-444.
[65] Ahuja, A., Dev, K., Tanwar, R.S. and Tyagi, P.K. (2014) Copper Mediated Neurological Disorder: Visions into Amyotrophic Lateral Sclerosis, Alzheimer and Menkes Disease. Journal of Trace Elements in Medicine and Biology, in Press.
[66] Squitti, R. (2012) Copper Dysfunction in Alzheimer’s Disease: From Meta-Analysis of Biochemical Studies to New Insight into Genetics. Journal of Trace Elements in Medicine and Biology, 26, 93-96.
[67] Brewer, G.J. (2012) Copper Toxicity in Alzheimer’s Disease: Cognitive Loss from Ingestion of Inorganic Copper. Journal of Trace Elements in Medicine and Biology, 26, 89-92.
[68] Angeletti, B., et al. (2005) BACE1 Cytoplasmic Domain Interacts with the Copper Chaperone for Superoxide Dismutase-1 and Binds Copper. Journal of Biological Chemistry, 280, 17930-17937.
[69] Sparks, D.L. and Schreurs, B.G. (2003) Trace Amounts of Copper in Water Induce β-Amyloid Plaques and Learning Deficits in a Rabbit Model of Alzheimer’s Disease. Proceedings of the National Academy of Sciences of the United States of America, 100, 11065-11069.
[70] Curtain, C.C., Ali, F.E., Smith, D.G., Bush, A.I., Masters, C.L. and Barnham, K.J. (2003) Metal Ions, pH, and Cholesterol Regulate the Interactions of Alzheimer’s Disease Amyloid-β Peptide with Membrane Lipid. Journal of Biological Chemistry, 278, 2977-2982.
[71] Eskici, G. and Axelsen, P.H. (2012) Copper and Oxidative Stress in the Pathogenesis of Alzheimer’s Disease. Biochemistry, 51, 6289-6311.
[72] Meloni, G., Sonois, V., Delaine, T., Guilloreau, L., Gillet, A., Teissié, J., et al. (2008) Metal Swap between Zn7-Metallothionein-3 and Amyloid-β-Cu Protects against Amyloid-β Toxicity. Nature Chemical Biology, 4, 366-372.
[73] Hung, Y.H., Robb, E.L., Volitakis, I., Ho, M., Evin, G., Li, Q.X., et al. (2009) Paradoxical Condensation of Copper with Elevated Beta-Amyloid in Lipid Rafts under Cellular Copper Deficiency Conditions: Implications for Alzheimer Disease. The Journal of Biological Chemistry, 284, 21899-21907.
[74] Singh, I., Sagare, A.P., Coma, M., Perlmutter, D., Gelein, R., Bell, R.D., et al. (2013) Low Levels of Copper Disrupt Brain Amyloid-β Homeostasis by Altering Its Production and Clearance. Proceedings of the National Academy of Sciences of the United States of America, 110, 14771-14776.
[75] Huang, X., et al. (1999) The Aβ Peptide of Alzheimer’s Disease Directly Produces Hydrogen Peroxide through Metal Ion Reduction. Biochemistry, 38, 7609-7616.
[76] Berridge, M.J. (2010) Calcium Hypothesis of Alzheimer’s Disease. Pflügers Archiv-European Journal of Physiology, 459, 441-449.
[77] Berridge, M.J. (2013) Dysregulation of Neural Calcium Signaling in Alzheimer Disease, Bipolar Disorder and Schizophrenia. Prion, 7, 2-13.
[78] Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., et al. (2001) Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer’s Disease Transgenic Mice. Neuron, 30, 665-676.
[79] Noël, S., Perez, F., Pedersen, J.T., Alies, B., Ladeira, S., Sayen, S., et al. (2012) A New Water-Soluble Cu(II) Chelator That Retrieves Cu from Cu (Amyloid-β) Species, Stops Associated ROS Production and Prevents Cu(II)-Induced Aβ Aggregation. Journal of Inorganic Biochemistry, 117, 322-325.
[80] Geng, J., Li, M., Wu, L., Ren, J. and Qu, X. (2012) Liberation of Copper from Amyloid Plaques: Making a Risk Factor Useful for Alzheimer’s Disease Treatment. Journal of Medicinal Chemistry, 55, 9146-9155.
[81] Matlack, K.E., Tardiff, D.F., Narayan, P., Hamamichi, S., Caldwell, K.A., Caldwell, G.A. and Lindquist, S. (2014) Clioquinol Promotes the Degradation of Metal-Dependent Amyloid-β (Aβ) Oligomers to Restore Endocytosis and Ameliorate Aβ Toxicity. Proceedings of the National Academy of Sciences of the United States of America, 111, 4013- 4018.
[82] Hua, H., Munter, L., Harmeier, A., Georgiev, O., Multhaup, G. and Schaffner, W. (2011) Toxicity of Alzheimer’s Disease-Associated Abeta Peptide Is Ameliorated in a Drosophila Model by Tight Control of Zinc and Copper Availability. Biological Chemistry, 392, 919-926.
[83] Baum, L. and Ng, A. (2004) Curcumin Interaction with Copper and Iron Suggests One Possible Mechanism of Action in Alzheimer’s Disease Animal Models. Journal of Alzheimer’s Disease, 6, 367-377.
[84] Picciano, A.L. and Vaden, T.D. (2013) Complexation between Cu(II) and Curcumin in the Presence of Two Different Segments of Amyloid β. Biophysical Chemistry, 184, 62-67.
[85] Huang, H.C., Lin, C.J., Liu, W.J., Jiang, R.R. and Jiang, Z.F. (2011) Dual Effects of Curcumin on Neuronal Oxidative Stress in the Presence of Cu(II). Food and Chemical Toxicology, 49, 1578-1583.
[86] Park, S.Y., Kim, H.S., Cho, E.K., Kwon, B.Y., Phark, S., Hwang, K.W. and Sul, D. (2008) Curcumin Protected PC12 Cells against Beta-Amyloid-Induced Toxicity through the Inhibition of Oxidative Damage and Tau Hyperphosphorylation. Food and Chemical Toxicology, 46, 2881-2887.
[87] Bayer, T.A., Schäfer, S., Simons, A., Kemmling, A., Kamer, T., Tepests, R., et al. (2003) Dietary Cu Stabilizes Brain Superoxide Dismutase 1 Activity and Reduces Amyloid Aβ Production in APP23 Transgenic Mice. Proceedings of the National Academy of Sciences of the United States of America, 100, 14187-14192.
[88] Klevay, L.M. (2008) Alzheimer’s Disease as Copper Deficiency. Medical Hypotheses, 70, 802-807.
[89] Cater, M., McInnes, K., Li, Q., Volitakis, I., La Fontaine, S., Mercer, J. and Bush, A. (2008) Intracellular Copper Deficiency Increases Amyloid-Beta Secretion by Diverse Mechanisms. Biochemical Journal, 412, 141-152.
[90] Smale, G., Nichols, N.R., Brady, D.R., Finch, C.E. and Horton, W.E. (1995) Evidence for Apoptotic Cell Death in Alzheimer’s Disease. Experimental Neurology, 133, 225-230.
[91] Suo, Z., Tan, J., Placzek, A., Crawford, F., Fang, C. and Mullan, M. (1998) Alzheimer’s β-Amyloid Peptides Induce Inflammatory Cascade in Human Vascular Cells: The Roles of Cytokines and CD40. Brain Research, 807, 110-117.
[92] Del Bo, R., Angeretti, N., Lucca, E., De Simoni, M.G. and Forloni, G. (1995) Reciprocal Control of Inflammatory Cytokines, IL-1 and IL-6, and β-Amyloid Production in Cultures. Neuroscience Letters, 188, 70-74.
[93] McGeer, P.L., Schulzer, M. and McGeer, E.G. (1996) Arthritis and Anti-Inflammatory Agents as Possible Protective factors for Alzheimer’s Disease A Review of 17 Epidemiologic Studies. Neurology, 47, 425-432.
[94] Griffin, W.S.T., Sheng, J.G., Roberts, G.W. and Mrak, R.E. (1995) Interleukin-1 Expression in Different Plaque Types in Alzheimer’s Disease: Significance in Plaque Evalution. Journal of Neuropathology & Experimental Neurology, 54, 276-281.
[95] Buxbaum, J.D., Oishi, M., Chen, H.I., Pinkas-Kramarski, R., Jaffe, E.A., Gandy, S.E. and Greengard, P. (1992) Cholinergic Agonists and Interleukin 1 Regulate Processing and Secretion of the Alzheimer Beta/A4 Amyloid Protein Precursor. Proceedings of the National Academy of Sciences of the United States of America, 89, 10075-10078.
[96] Goldgaber, D., Harris, H.W., Hla, T., Maciag, T., Donnelly, R.J., Jacobsen, J.S., et al. (1989) Interleukin 1 Regulates Synthesis of Amyloid Beta-Protein Precursor mRNA in Human Endothelial Cells. Proceedings of the National Academy of Sciences of the United States of America, 86, 7606-7610.
[97] Trepanier, C.H. and Milgram, N.W. (2010) Neuroinflammation in Alzheimer’s Disease: Are NSAIDs and Selective COX-2 Inhibitors the Next Line of Therapy? Journal of Alzheimer’s Disease, 21, 1089-1099.
[98] Kalinski, T., Sel, S., Hütten, H., Röpke, M., Roessner, A. and Nass, N. (2014) Curcumin Blocks Interleukin-1 Signaling in Chondrosarcoma Cells. PLoS ONE, 9, e99296.
[99] Ahmed, T. and Gilani, A.H. (2011) A Comparative Study of Curcuminoids to Measure Their Effect on Inflammatory and Apoptotic Gene Expression in an Aβ plus Ibotenic Acid-Infused Rat Model of Alzheimer’s Disease. Brain Research, 1400, 1-18.
[100] Qin, X.Y., Cheng, Y. and Yu, L.C. (2010) Potential Protection of Curcumin against Intracellular Amyloid β-Induced Toxicity in Cultured Rat Prefrontal Cortical Neurons. Neuroscience Letters, 480, 21-24.
[101] Allan Butterfield, D., Castegna, A., Lauderback, C.M. and Drake, J. (2002) Evidence That Amyloid Beta-Peptide-Induced Lipid Peroxidation and Its Sequelae in Alzheimer’s Disease Brain Contribute to Neuronal Death. Neurobiology of Aging, 23, 655-664.
[102] Butterfield, D.A. and Lauderback, C.M. (2002) Lipid Peroxidation and Protein Oxidation in Alzheimer’s Disease Brain: Potential Causes and Consequences Involving Amyloid β-Peptide-Associated Free Radical Oxidative Stress. Free Radical Biology and Medicine, 32, 1050-1060.
[103] Behl, C. (1999) Alzheimer’s Disease and Oxidative Stress: Implications for Novel Therapeutic Approaches. Progress in Neurobiology, 57, 301-323.
[104] Butterfield, D.A., Swomley, A.M. and Sultana, R. (2013) Amyloid β-Peptide (1-42)-Induced Oxidative Stress in Alzheimer Disease: Importance in Disease Pathogenesis and Progression. Antioxidants & Redox Signaling, 19, 823-835.
[105] Allan Butterfield, D. (2002) Amyloid β-Peptide (1-42)-Induced Oxidative Stress and Neurotoxicity: Implications for Neurodegeneration in Alzheimer’s Disease Brain. A Review. Free Radical Research, 36, 1307-1313.
[106] Jena, S., Dandapat, J. and Chainy, G.B.N. (2013) Curcumin Differentially Regulates the Expression of Superoxide Dismutase in Cerebral Cortex and Cerebellum of l-Thyroxine (T4)-Induced Hyperthyroid Rat Brain. Neurological Sciences, 34, 505-510.
[107] Huang, H.C., Chang, P., Dai, X.L. and Jiang, Z.F. (2012) Protective Effects of Curcumin on Amyloid-β-Induced Neuronal Oxidative Damage. Neurochemical Research, 37, 1584-1597.
[108] Cassimeris, L. and Spittle, C. (2001) Regulation of Microtubule-Associated Proteins. International Review of Cytology, 210, 163-226.
[109] Wittmann, C.W., Wszolek, M.F., Shulman, J.M., Salvaterra, P.M., Lewis, J., Hutton, M. and Feany, M.B. (2001) Tauopathy in Drosophila: Neurodegeneration without Neurofibrillary Tangles. Science, 293, 711-714.
[110] Iba, M., Guo, J.L., McBride, J.D., Zhang, B., Trojanowski, J.Q. and Lee, V.M.Y. (2013) Synthetic Tau Fibrils Mediate Transmission of Neurofibrillary Tangles in a Transgenic Mouse Model of Alzheimer’s-Like Tauopathy. The Journal of Neuroscience, 33, 1024-1037.
[111] Ittner, L.M. and Götz, J. (2010) Amyloid-β and Tau—A Toxic pas de Deux in Alzheimer’s Disease. Nature Reviews. Neuroscience, 12, 65-72.
[112] Rapoport, M., Dawson, H.N., Binder, L.I., Vitek, M.P. and Ferreira, A. (2002) Tau Is Essential to β-Amyloid-Induced Neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 99, 6364-6369.
[113] Bloom, G.S. (2014) Amyloid-β and Tau: The Trigger and Bullet in Alzheimer Disease Pathogenesis. JAMA Neurology, 71, 505-508.
[114] Medina, M. and Avila, J. (2014) New Perspectives on the Role of Tau in Alzheimer’s Disease. Implications for Therapy. Biochemical Pharmacology, 88, 540-547.
[115] Mutsuga, M., Chambers, J.K., Uchida, K., Tei, M., Makibuchi, T., Mizorogi, T., et al. (2012) Binding of Curcumin to Senile Plaques and Cerebral Amyloid Angiopathy in the Aged Brain of Various Animals and to Neurofibrillary Tangles in Alzheimer’s Brain. The Journal of Veterinary Medical Science, 74, 51-57.
[116] Villaflores, O.B., Chen, Y.J., Chen, C.P., Yeh, J.M. and Wu, T.Y. (2012) Effects of Curcumin and Demethoxycurcumin on Amyloid-β Precursor and Tau Proteins through the Internal Ribosome Entry Sites: A Potential Therapeutic for Alzheimer’s Disease. Taiwanese Journal of Obstetrics and Gynecology, 51, 554-564.
[117] Ma, Q.L., Zuo, X., Yang, F., Ubeda, O.J., Gant, D.J., Alaverdyan, M., et al. (2013) Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice. Journal of Biological Chemistry, 288, 4056-4065.
[118] Belkacemi, A., Doggui, S., Dao, L. and Ramassamy, C. (2011) Challenges Associated with Curcumin Therapy in Alzheimer Disease. Expert Reviews in Molecular Medicine, 13, e34.
[119] Prasad, S., Tyagi, A.K. and Aggarwal, B.B. (2014) Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: The Golden Pigment from Golden Spice. Cancer Research and Treatment, 46, 2-18.
[120] Yang, K.Y., Lin, L.C., Tseng, T.Y., Wang, S.C. and Tsai, T.H. (2007) Oral Bioavailability of Curcumin in Rat and the Herbal Analysis from Curcuma longa by LC-MS/MS. Journal of Chromatography B, 853, 183-189.
[121] Jang, D.J., Kim, S.T., Oh, E. and Lee, K. (2014) Enhanced Oral Bioavailability and Antiasthmatic Efficacy of Curcumin Using Redispersible Dry Emulsion. Bio-Medical Materials and Engineering, 24, 917-930.
[122] Shelma, R. and Sharma, C.P. (2013) In Vitro and in Vivo Evaluation of Curcumin Loaded Lauroyl Sulphated Chitosan for Enhancing Oral Bioavailability. Carbohydrate Polymers, 95, 441-448.
[123] Li, C., Zhang, Y., Su, T., Feng, L., Long, Y. and Chen, Z. (2012) Silica-Coated Flexible Liposomes as a Nanohybrid Delivery System for Enhanced Oral Bioavailability of Curcumin. International Journal of Nanomedicine, 7, 5995-6002.
[124] Holder, G.M., Plummer, J.L. and Ryan, A.J. (1978) The Metabolism and Excretion of Curcumin (1,7-Bis-(4-hydroxy- 3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the Rat. Xenobiotica, 8, 761-768.
[125] Pan, M.H., Huang, T.M. and Lin, J.K. (1999) Biotransformation of Curcumin through Reduction and Glucuronidation in Mice. Drug Metabolism and Disposition, 27, 486-494.
[126] Ireson, C., Orr, S., Jones, D.J., Verschoyle, R., Lim, C.K., Luo, J.L., et al. (2001) Char-Acterization of Metabolites of the Chemopreventive Agent Curcumin in Human and Rat Hepatocytes and in the Rat in Vivo, and Evaluation of Their Ability to Inhibit Phorbol Ester-Induced Prostaglandin E2 Production. Cancer Research, 61, 1058-1064.
[127] Pan, M.H., Lin-Shiau, S.Y. and Lin, J.K. (2000) Comparative Studies on the Suppression of Nitric Oxide Synthase by Curcumin and Its Hydrogenated Metabolites through Down-Regulation of IkappaB Kinase and NFkappaB Activation in Macrophages. Biochemical Pharmacology, 60, 1665-1676.
[128] Baum, L., Lam, C.W.K., Cheung, S.K.K., Kwok, T., Lui, V., Tsoh, J., et al. (2008) Six-Month Randomized, Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in Patients with Alzheimer Disease. Journal of Clinical Psychopharmacology, 28, 110-113.
[129] Ringman, J.M., Frautschy, S.A., Teng, E., Begum, A.N., Bardens, J., Beigi, M., et al. (2012) Oral Curcumin for Alzheimer’s Disease: Tolerability and Efficacy in a 24-Week Randomized, Double Blind, Placebo-Controlled Study. Alzheimer’s Research & Therapy, 4, 43-43.
[130] Baum, L., Cheung, S.K., Mok, V.C., Lam, L.C., Leung, V.P., Hui, E., et al. (2007) Curcumin Effects on Blood Lipid Profile in a 6-Month Human Study. Pharmacological Research, 56, 509-514.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.