All Title Author
Keywords Abstract

Transthyretin—A Key Gene Involved in Regulating Learning and Memory in Brain, and Providing Neuroprotection in Alzheimer Disease via Neuronal Synthesis of Transthyretin Protein

DOI: 10.4236/jbbs.2018.82005, PP. 77-92

Keywords: Learning and Memory, TTR—Transthyretin, AD—Alzheimer Disease, CSF—Cerebrospinal Fluid, MAPK—Mitogen-Activated Protein Kinases, CREB—cAMP Response Element Binding Protein, ERK—Extracellular Receptor Kinases, Aβ—Amyloid Beta, LTP—Long-Term Potentiation, LTD—Long-Term Depression

Full-Text   Cite this paper   Add to My Lib


Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions; by which mechanisms it promotes neurite outgrowth; and how it protects the brain from Alzheimer disease (AD).


[1]  Ribeiro, C.A., et al. (2014) Transthyretin Stabilization by Iododiflunisal Promotes Amyloid-Beta Peptide Clearance, Decreases Its Deposition, and Ameliorates Cognitive Deficits in an Alzheimer's Disease Mouse Model. Journal of Alzheimer’s Disease, 39, 357-370.
[2]  Palha, J.A. (2002) Transthyretin as a Thyroid Hormone Carrier: Function Revisited. Clinical Chemistry and Laboratory Medicine, 40, 1292-1300.
[3]  Sousa, J.C., et al. (2007) Transthyretin Influences Spatial Reference Memory. Neurobiology of Learning and Memory, 88, 381-385.
[4]  Bauer, M., Heinz, A. and Whybrow, P.C. (2002) Thyroid Hormones, Serotonin and Mood: Of Synergy and Significance in the Adult Brain. Molecular Psychiatry, 7, 140-156.
[5]  Dickson, P.W. and Schreiber, G. (1986) High Levels of Messenger RNA for Transthyretin (Prealbumin) in Human Choroid Plexus. Neuroscience Letters, 66, 311-315.
[6]  Southwell, B.R., et al. (1993) Thyroxine Transport to the Brain: Role of Protein Synthesis by the Choroid Plexus. Endocrinology, 133, 2116-2126.
[7]  Hu, S., Loo, J.A. and Wong, D.T. (2006) Human Body Fluid Proteome Analysis. Proteomics, 6, 6326-6353.
[8]  Kassem, N.A., et al. (2006) Role of Transthyretin in Thyroxine Transfer from Cerebrospinal Fluid to Brain and Choroid Plexus. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 291, R1310-R1315.
[9]  Chen, R.L., Kassem, N.A. and Preston, J.E. (2006) Dose-Dependent Transthyretin Inhibition of T4 Uptake from Cerebrospinal Fluid in Sheep. Neuroscience Letters, 396, 7-11.
[10]  Chen, R., Chen, C.P. and Preston, J.E. (2016) Effects of Transthyretin on Thyroxine and Beta-Amyloid Removal from Cerebrospinal Fluid in Mice. Clinical and Experimental Pharmacology & Physiology, 43, 844-850.
[11]  Suzuyama, K., et al. (2004) Combined Proteomic Approach with SELDI-TOF-MS and Peptide Mass Fingerprinting Identified the Rapid Increase of Monomeric Transthyretin in Rat Cerebrospinal Fluid after Transient Focal Cerebral Ischemia. Molecular Brain Research, 129, 44-53.
[12]  Schwarzman, A.L., et al. (1994) Transthyretin Sequesters Amyloid Beta Protein and Prevents Amyloid Formation. Proceedings of the National Academy of Sciences of the United States of America, 91, 8368-8372.
[13]  Li, X., et al. (2013) Mechanisms of Transthyretin Inhibition of Beta-Amyloid Aggregation in vitro. Journal of Neuroscience, 33, 19423-19433.
[14]  Yang, D.T., et al. (2013) Transthyretin as Both a Sensor and a Scavenger of Beta-Amyloid Oligomers. Biochemistry, 52, 2849-2861.
[15]  Schultz, K., Traskman-Bendz, L. and Petersen, A. (2008) Transthyretin in Cerebrospinal Fluid from Suicide Attempters. Journal of Affective Disorders, 109, 205-208.
[16]  Alemi, M., et al. (2016) Transthyretin Participates in Beta-Amyloid Transport from the Brain to the Liver—Involvement of the Low-Density Lipoprotein Receptor-Related Protein 1? Scientific Reports, 6, Article Number: 20164.
[17]  Oliveira, S.M., et al. (2011) Gender-Dependent Transthyretin Modulation of Brain Amyloid-Beta Levels: Evidence from a Mouse Model of Alzheimer’s Disease. Journal of Alzheimer’s Disease, 27, 429-439.
[18]  Costa, R., et al. (2008) Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor. PLoS ONE, 3, e2899.
[19]  Alshehri, B., et al. (2015) The Diversity of Mechanisms Influenced by Transthyretin in Neurobiology: Development, Disease and Endocrine Disruption. Journal of Neuroendocrinology, 27, 303-323.
[20]  Fleming, C.E., et al. (2009) Transthyretin Internalization by Sensory Neurons Is Megalin Mediated and Necessary for Its Neuritogenic Activity. Journal of Neuroscience, 29, 3220-3232.
[21]  Goncalves, N.P., Teixeira-Coelho, M. and Saraiva, M.J. (2015) Protective Role of Anakinra against Transthyretin-Mediated Axonal Loss and Cell Death in a Mouse Model of Familial Amyloidotic Polyneuropathy. Journal of Neuropathology & Experimental Neurology, 74, 203-217.
[22]  Doggui, S., et al. (2010) Possible Involvement of Transthyretin in Hippocampal Beta-Amyloid Burden and Learning Behaviors in a Mouse Model of Alzheimer’s Disease (TgCRND8). Neurodegenerative Diseases, 7, 88-95.
[23]  Gomes, J.R., et al. (2016) Transthyretin Provides Trophic Support via Megalin by Promoting Neurite Outgrowth and Neuroprotection in Cerebral Ischemia. Cell Death and Differentiation, 23, 1749-1764.
[24]  Alvira-Botero, X., et al. (2010) Megalin Interacts with APP and the Intracellular Adapter Protein FE65 in Neurons. Molecular and Cellular Neuroscience, 45, 306-315.
[25]  Fleming, C.E., et al. (2009) Chapter 17: Transthyretin: An Enhancer of Nerve Regeneration. International Review of Neurobiology, 87, 337-346.
[26]  Santos, S.D., et al. (2010) CSF Transthyretin Neuroprotection in a Mouse Model of Brain Ischemia. Journal of Neurochemistry, 115, 1434-1444.
[27]  Gao, C., et al. (2011) Serum Prealbumin (Transthyretin) Predict Good Outcome in Young Patients with Cerebral Infarction. Clinical and Experimental Medicine, 11, 49-54.
[28]  Quintela, T., et al. (2009) 17Beta-Estradiol Induces Transthyretin Expression in Murine Choroid Plexus via an Oestrogen Receptor Dependent Pathway. Cellular and Molecular Neurobiology, 29, 475-483.
[29]  Garzuly, F., et al. (1996) Familial Meningocerebrovascular Amyloidosis, Hungarian Type, with Mutant Transthyretin (TTR Asp18Gly). Neurology, 47, 1562-1567.
[30]  Sousa, M.M. and Saraiva, M.J. (2001) Internalization of Transthyretin. Evidence of a Novel yet Unidentified Receptor-Associated Protein (RAP)-Sensitive Receptor. The Journal of Biological Chemistry, 276, 14420-14425.
[31]  Wang, X., et al. (2010) Caenorhabditis elegans Transthyretin-Like Protein TTR-52 Mediates Recognition of Apoptotic Cells by the CED-1 Phagocyte Receptor. Nature Cell Biology, 12, 655-664.
[32]  Sousa, M.M., et al. (2000) Evidence for the Role of Megalin in Renal Uptake of Transthyretin. The Journal of Biological Chemistry, 275, 38176-38181.
[33]  Sousa, M.M., et al. (2000) Interaction of the Receptor for Advanced Glycation End Products (RAGE) with Transthyretin Triggers Nuclear Transcription Factor kB (NF-kB) Activation. Laboratory Investigation, 80, 1101-1110.
[34]  Vieira, M., Gomes, J.R. and Saraiva, M.J. (2015) Transthyretin Induces Insulin-Like Growth Factor I Nuclear Translocation Regulating Its Levels in the Hippocampus. Molecular Neurobiology, 51, 1468-1479.
[35]  Marzolo, M.P. and Farfan, P. (2011) New Insights into the Roles of Megalin/LRP2 and the Regulation of Its Functional Expression. Biological Research, 44, 89-105.
[36]  Mantuano, E., et al. (2008) Molecular Dissection of the Human Alpha2-Macroglobulin Subunit Reveals Domains with Antagonistic Activities in Cell Signaling. The Journal of Biological Chemistry, 283, 19904-19911.
[37]  Salter, M.W. and Kalia, L.V. (2004) Src Kinases: A Hub for NMDA Receptor Regulation. Nature Reviews Neuroscience, 5, 317-328.
[38]  Nunes, A.F., et al. (2009) Transthyretin Knockout Mice Display Decreased Susceptibility to AMPA-Induced Neurodegeneration. Neurochemistry International, 55, 454-457.
[39]  Lai, T.W., Zhang, S. and Wang, Y.T. (2014) Excitotoxicity and Stroke: Identifying Novel Targets for Neuroprotection. Progress in Neurobiology, 115, 157-188.
[40]  Hill, M.D., et al. (2012) Safety and Efficacy of NA-1 in Patients with Iatrogenic Stroke after Endovascular Aneurysm Repair (ENACT): A Phase 2, Randomised, Double-Blind, Placebo-Controlled Trial. The Lancet Neurology, 11, 942-950.
[41]  Szydlowska, K. and Tymianski, M. (2010) Calcium, Ischemia and Excitotoxicity. Cell Calcium, 47, 122-129.
[42]  Neumann, B., et al. (2015) EFF-1-Mediated Regenerative Axonal Fusion Requires Components of the Apoptotic Pathway. Nature, 517, 219-222.
[43]  Fleming, C.E., Saraiva, M.J. and Sousa, M.M. (2007) Transthyretin Enhances Nerve Regeneration. Journal of Neurochemistry, 103, 831-839.
[44]  Mattson, M.P. and Magnus, T. (2006) Ageing and Neuronal Vulnerability. Nature Reviews Neuroscience, 7, 278-294.
[45]  Kandel, E.R. (2001) The Molecular Biology of Memory Storage: A Dialogue between Genes and Synapses. Science, 294 1030-1038.
[46]  Silva, A.J. (2003) Molecular and Cellular Cognitive Studies of the Role of Synaptic Plasticity in Memory. Journal of Neurobiology, 54, 224-237.
[47]  Gonzalez-Marrero, I., et al. (2015) Choroid Plexus Dysfunction Impairs Beta-Amyloid Clearance in a Triple Transgenic Mouse Model of Alzheimer’s Disease. Frontiers in Cellular Neuroscience, 9, 17.
[48]  Bach, M.E., et al. (1999) Age-Related Defects in Spatial Memory Are Correlated with Defects in the Late Phase of Hippocampal Long-Term Potentiation in vitro and Are Attenuated by Drugs That Enhance the cAMP Signaling Pathway. Proceedings of the National Academy of Sciences of the United States of America, 96, 5280-5285.
[49]  Tombaugh, G.C., et al. (2002) Theta-Frequency Synaptic Potentiation in CA1 in vitro Distinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats. The Journal of Neuroscience, 22, 9932-9940.
[50]  Hollup, S.A., et al. (2001) Impaired Recognition of the Goal Location during Spatial Navigation in Rats with Hippocampal Lesions. The Journal of Neuroscience, 21, 4505-4513.
[51]  Blalock, E.M., et al. (2003) Gene Microarrays in Hippocampal Aging: Statistical Profiling Identifies Novel Processes Correlated with Cognitive Impairment. The Journal of Neuroscience, 23, 3807-3819.
[52]  Lu, T., et al. (2004) Gene Regulation and DNA Damage in the Ageing Human Brain. Nature, 429, 883-891.
[53]  Verbitsky, M., et al. (2004) Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice. Learning & Memory, 11, 253-260.
[54]  Stemmelin, J., et al. (2000) Immunohistochemical and Neurochemical Correlates of Learning Deficits in Aged Rats. Neuroscience, 96, 275-289.
[55]  Igaz, L.M., et al. (2002) Two Time Periods of Hippocampal mRNA Synthesis Are Required for Memory Consolidation of Fear-Motivated Learning. The Journal of Neuroscience, 22, 6781-6789.
[56]  Brouillette, J. and Quirion, R. (2008) Transthyretin: A Key Gene Involved in the Maintenance of Memory Capacities during Aging. Neurobiology of Aging, 29, 1721-1732.
[57]  Monaco, H.L. (2000) The Transthyretin-Retinol-Binding Protein Complex. Biochimica et Biophysica Acta, 1482, 65-72.
[58]  Misner, D.L., et al. (2001) Vitamin A Deprivation Results in Reversible Loss of Hippocampal Long-Term Synaptic Plasticity. Proceedings of the National Academy of Sciences of the United States of America, 98, 11714-11719.
[59]  Etchamendy, N., et al. (2001) Alleviation of a Selective Age-Related Relational Memory Deficit in Mice by Pharmacologically Induced Normalization of Brain Retinoid Signaling. The Journal of Neuroscience, 21, 6423-6429.
[60]  Cocco, S., et al. (2002) Vitamin A Deficiency Produces Spatial Learning and Memory Impairment in Rats. Neuroscience, 115, 475-482.
[61]  Chen, A., et al. (2003) Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins. Neuron, 39, 655-669.
[62]  Mouravlev, A., et al. (2006) Somatic Gene Transfer of cAMP Response Element-Binding Protein Attenuates Memory Impairment in Aging Rats. Proceedings of the National Academy of Sciences of the United States of America, 103, 4705-4710.
[63]  Jacobs, S., et al. (2006) Retinoic Acid Is Required Early during Adult Neurogenesis in the Dentate Gyrus. Proceedings of the National Academy of Sciences of the United States of America, 103, 3902-3907.
[64]  Snyder, J.S., et al. (2005) A Role for Adult Neurogenesis in Spatial Long-Term Memory. Neuroscience, 130, 843-852.
[65]  von Bohlen und Halbach, O., et al. (2006) Age-Related Alterations in Hippocampal Spines and Deficiencies in Spatial Memory in Mice. Journal of Neuroscience Research, 83, 525-531.
[66]  Jacobsen, J.S., et al. (2006) Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 103, 5161-5166.
[67]  Cerqueira, J.J., et al. (2007) The Prefrontal Cortex as a Key Target of the Maladaptive Response to Stress. The Journal of Neuroscience, 27, 2781-2787.
[68]  Sousa, J.C., et al. (2007) Transthyretin and Alzheimer’s Disease: Where in the Brain? Neurobiology of Aging, 28, 713-718.
[69]  Lavado-Autric, R., et al. (2003) Early Maternal Hypothyroxinemia Alters Histogenesis and Cerebral Cortex Cytoarchitecture of the Progeny. The Journal of Clinical Investigation, 111, 1073-1082.
[70]  Gilbert, M.E. and Sui, L. (2006) Dose-Dependent Reductions in Spatial Learning and Synaptic Function in the Dentate Gyrus of Adult Rats Following Developmental Thyroid Hormone Insufficiency. Brain Research, 1069, 10-22.
[71]  Schafer, M.J., et al. (2015) Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures. PLoS ONE, 10, e0133923.
[72]  Benoit, C.E., et al. (2011) Genomic and Proteomic Strategies to Identify Novel Targets Potentially Involved in Learning and Memory. Trends in Pharmacological Sciences, 32, 43-52.
[73]  Nunes, A.F., Saraiva, M.J. and Sousa, M.M. (2006) Transthyretin Knockouts Are a New Mouse Model for Increased Neuropeptide Y. The FASEB Journal, 20, 166-168.
[74]  Thorsell, A., et al. (2000) Behavioral Insensitivity to Restraint Stress, Absent Fear Suppression of Behavior and Impaired Spatial Learning in Transgenic Rats with Hippocampal Neuropeptide Y Overexpression. Proceedings of the National Academy of Sciences of the United States of America, 97, 12852-12857.
[75]  Vieira, M. and Saraiva, M.J. (2013) Transthyretin Regulates Hippocampal 14-3-3 Zeta Protein Levels. FEBS Letters, 587, 1482-1488.
[76]  Schindler, C.K., Heverin, M. and Henshall, D.C. (2006) Isoform- and Subcellular Fraction-Specific Differences in Hippocampal 14-3-3 Levels Following Experimentally Evoked Seizures and in Human Temporal Lobe Epilepsy. Journal of Neurochemistry, 99, 561-569.
[77]  Heverin, M., et al. (2012) Proteomic Analysis of 14-3-3 Zeta Binding Proteins in the Mouse Hippocampus. International Journal of Physiology, Pathophysiology and Pharmacology, 4, 74-83.
[78]  VanGuilder, H.D., et al. (2011) Hippocampal Dysregulation of Synaptic Plasticity-Associated Proteins with Age-Related Cognitive Decline. Neurobiology of Disease, 43, 201-212.
[79]  Pozuelo-Rubio, M. (2011) 14-3-3Zeta Binds Class III Phosphatidylinositol-3-Kinase and Inhibits Autophagy. Autophagy, 7, 240-242.
[80]  Pozuelo-Rubio, M. (2011) Regulation of Autophagic Activity by 14-3-3Zeta Proteins Associated with Class III Phosphatidylinositol-3-Kinase. Cell Death and Differentiation, 18, 479-492.
[81]  Rajawat, Y., Hilioti, Z. and Bossis, I. (2010) Autophagy: A Target for Retinoic Acids. Autophagy, 6, 1224-1226.
[82]  Rajawat, Y., Hilioti, Z. and Bossis, I. (2011) Retinoic Acid Induces Autophagosome Maturation through Redistribution of the Cation-Independent Mannose-6-Phosphate Receptor. Antioxidants & Redox Signaling, 14, 2165-2177.
[83]  Philip, N., Acevedo, S.F. and Skoulakis, E.M. (2001) Conditional Rescue of Olfactory Learning and Memory Defects in Mutants of the 14-3-3Zeta Gene Leonardo. The Journal of Neuroscience, 21, 8417-8425.
[84]  Cheah, P.S., et al. (2012) Neurodevelopmental and Neuropsychiatric Behaviour Defects Arise from 14-3-3Zeta Deficiency. Molecular Psychiatry, 17,451-466.
[85]  Dickson, D.W. (2004) Apoptotic Mechanisms in Alzheimer Neurofibrillary Degeneration: Cause or Effect? The Journal of Clinical Investigation, 114, 23-27.
[86]  Kang, J., et al. (1987) The Precursor of Alzheimer’s Disease Amyloid A4 Protein Resembles a Cell-Surface Receptor. Nature, 325, 733-736.
[87]  Philibert, K.D., et al. (2014) Identification and Characterization of ABeta Peptide Interactors in Alzheimer’s Disease by Structural Approaches. Frontiers in Aging Neuroscience, 6, 265.
[88]  Selkoe, D.J. (2001) Clearing the Brain’s Amyloid Cobwebs. Neuron, 32, 177-180.
[89]  Cho, P.Y., et al. (2015) A Cyclic Peptide Mimic of the Beta-Amyloid Binding Domain on Transthyretin. ACS Chemical Neuroscience, 6, 778-789.
[90]  Ankarcrona, M., et al. (2016) Current and Future Treatment of Amyloid Diseases. The Journal of Internal Medicine, 280, 177-202.
[91]  Crossgrove, J.S., Li, G.J. and Zheng, W. (2005) The Choroid Plexus Removes Beta-Amyloid from Brain Cerebrospinal Fluid. Experimental Biology and Medicine (Maywood), 230, 771-776.
[92]  Crossgrove, J.S., Smith, E.L. and Zheng, W. (2007) Macromolecules Involved in Production and Metabolism of Beta-Amyloid at the Brain Barriers. Brain Research, 1138, 187-195.
[93]  Ingenbleek, Y. and Bernstein, L.H. (2015) Downsizing of Lean Body Mass Is a Key Determinant of Alzheimer’s Disease. Journal of Alzheimer’s Disease, 44, 745-754.
[94]  Tsai, K.J., et al. (2009) Asymmetric Expression Patterns of Brain Transthyretin in Normal Mice and a Transgenic Mouse Model of Alzheimer’s Disease. Neuroscience, 159, 638-646.
[95]  Merched, A., et al. (1998) Apolipoprotein E, Transthyretin and Actin in the CSF of Alzheimer’s Patients: Relation with the Senile Plaques and Cytoskeleton Biochemistry. FEBS Letters, 425, 225-228.
[96]  Stein, T.D. and Johnson, J.A. (2002) Lack of Neurodegeneration in Transgenic Mice Overexpressing Mutant Amyloid Precursor Protein Is Associated with Increased Levels of Transthyretin and the Activation of Cell Survival Pathways. Journal of Neuroscience, 22, 7380-7388.
[97]  Serot, J.M., et al. (1997) Cerebrospinal Fluid Transthyretin: Aging and Late Onset Alzheimer’s disease. The Journal of Neurology, Neurosurgery, and Psychiatry, 63, 506-508.
[98]  Castano, E.M., et al. (2006) Comparative Proteomics of Cerebrospinal Fluid in Neuropathologically-Confirmed Alzheimer’s Disease and Non-Demented Elderly Subjects. Neurological Research, 28, 155-163.
[99]  Gloeckner, S.F., et al. (2008) Quantitative Analysis of Transthyretin, Tau and Amyloid-Beta in Patients with Dementia. The Journal of Alzheimer’s Disease, 14, 17-25.
[100]  Hansson, S.F., et al. (2009) Reduced Levels of Amyloid-Beta-Binding Proteins in Cerebrospinal Fluid from Alzheimer’s Disease Patients. The Journal of Alzheimer’s Disease, 16, 389-397.
[101]  Chodobski, A. and Szmydynger-Chodobska, J. (2001) Choroid Plexus: Target for Polypeptides and Site of Their Synthesis. Microscopy Research and Technique, 52, 65-82.<65::AID-JEMT9>3.0.CO;2-4
[102]  Geroldi, C., et al. (2000) Temporal Lobe Asymmetry in Patients with Alzheimer’s Disease with Delusions. The Journal of Neurology, Neurosurgery, and Psychiatry, 69, 187-191.
[103]  Lein, E.S., et al. (2007) Genome-Wide Atlas of Gene Expression in the Adult Mouse Brain. Nature, 445, 168-176.
[104]  Santos, L.M., et al. (2016) Resveratrol Administration Increases Transthyretin Protein Levels Ameliorating AD Features—Importance of Transthyretin Tetrameric Stability. Molecular Medicine, 22, 28.
[105]  Maetani, Y., et al. (2016) Familial Amyloid Polyneuropathy Involving a Homozygous Val30Met Mutation in the Amyloidogenic Transthyretin Gene Presenting with Superficial Siderosis: A Case Report. Rinsho Shinkeigaku, 56, 430-434.
[106]  Li, X. and Buxbaum, J.N. (2011) Transthyretin and the Brain Re-Visited: Is Neuronal Synthesis of Transthyretin Protective in Alzheimer’s Disease? Molecular Neurodegeneration, 6, 79.
[107]  Dewachter, I., et al. (2000) Aging Increased Amyloid Peptide and Caused Amyloid Plaques in Brain of Old APP/V717I Transgenic Mice by a Different Mechanism than Mutant Presenilin1. Journal of Neuroscience, 20, 6452-6458.
[108]  Natunen, T., et al. (2012) Genetic Analysis of Genes Involved in Amyloid-Beta Degradation and Clearance in Alzheimer’s Disease. The Journal of Alzheimer’s Disease, 28, 553-559.
[109]  Bergen, A.A., et al. (2015) Gene Expression and Functional Annotation of Human Choroid Plexus Epithelium Failure in Alzheimer’s Disease. BMC Genomics, 16, 956.
[110]  Bastianetto, S., Brouillette, J. and Quirion, R. (2007) Neuroprotective Effects of Natural Products: Interaction with Intracellular Kinases, Amyloid Peptides and a Possible Role for Transthyretin. Neurochemical Research, 32, 1720-1725.


comments powered by Disqus