Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2018, Vol. 9 Issue (3) : 523-536     DOI: 10.14336/AD.2017.0717
Review Article |
BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders
Shen Ting1,*, You Yuyi2, Joseph Chitra1, Mirzaei Mehdi3, Klistorner Alexander1,2, Graham Stuart L.1,2, Gupta Vivek1
1Faculty of Medicine and Health Sciences, Macquarie University, Australia
2Save Sight Institute, Sydney University, Sydney, Australia
3Faculty of Science and Engineering, Macquarie University, Australia
Download: PDF(469 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Brain-derived neurotrophic factor (BDNF) has a unique role in the neuronal development, differentiation, and survival in the developing and adult nervous system. A common single-nucleotide polymorphism in the pro-region of the human BDNF gene, resulting in a valine to methionine substitution (Val66Met), has been associated with the susceptibility, incidence, and clinical features of several neurodegenerative disorders. Much research has been dedicated to evaluating the effects of polymorphism in the past decade, and functional effects of this genetic variation. A better understanding of how this naturally occurring polymorphism associates with or influences physiology, anatomy, and cognition in both healthy and diseased adults in neurodegenerative conditions will help understand neurochemical mechanisms and definable clinical outcomes in humans. Here we review the role and relevance of the BDNF Val66Met polymorphism in neurodegenerative diseases, with particular emphasis on glaucoma, multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several controversies and unresolved issues, including small effect sizes, possible ethnicity, gender, and age effects of the BDNF Val66Met are also discussed with respect to future research.

Keywords BDNF      polymorphism      neurodegenerative diseases      glaucoma      multiple sclerosis      Alzheimer’s disease     
Corresponding Authors: Shen Ting (current email address: tingshen313@outlook.com)   
About author: These authors have contributed equally to this work.
Issue Date: 05 June 2018
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Shen Ting
You Yuyi
Joseph Chitra
Mirzaei Mehdi
Klistorner Alexander
Graham Stuart L.
Gupta Vivek
Cite this article:   
Shen Ting,You Yuyi,Joseph Chitra, et al. BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders[J]. Aging and disease, 2018, 9(3): 523-536.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2017.0717     OR     http://www.aginganddisease.org/EN/Y2018/V9/I3/523
EthnicityCohortTotal NReferenceAllele frequencyGenotype
A (Met) %G (Val) %A/A (Met/Met) %G/A (Val/Met) %G/G (Val/Val) %
AsianKorea244Pivac et al. 200946.353.723.445.930.7
Japan657Fukumoto et al. 200939.061.015.047.038.0
Japan275Nishimura et al. 200942.557.517.150.932.0
China239Bian et al. 200545.454.621.348.130.5
Japan471Matsushita et al. 200544.555.520.847.431.9
Japan151Itoh et al. 200341.158.915.950.333.8
CaucasianRomania1124Vulturar et al. 201619.380.74.030.565.5
Poland193Nowak et al. 201415.085.01.030.069.0
Croatia556Pivac et al. 200919.580.53.432.464.2
Italy233Guerini et al. 200920.679.44.332.663.1
Italy37Liguori et al. 200917.682.42.729.767.6
USA250Zhang et al. 200618.881.24.029.666.4
Finland920Vepsalainen et al. 200513.087.02.024.075.0
USA194Bodner et al. 200519.081.03.032.264.7
USA392Parsian et al. 200428.072.02.053.045.0
Spain218Combarros et al. 200419.081.03.730.765.6
USA133Egan et al. 200318.082.04.527.168.4
Italy111Ventriglia et al. 200129.770.38.143.248.7
Table 1  Allele and genotype distributions for the Val66Met polymorphism of Brain-derived neurotrophic factor (BDNF) in healthy subjects in different ethnicity.
Figure 1.  Changes in Brain-derived neurotrophic factor (BDNF) protein levels and BDNF Val66Met polymorphism as modifiers of neurodegenerative disorders and psychiatric disorders.
[1] Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112: 257-269
[2] Notaras M, Hill R, van den Buuse M (2015). The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy. Mol Psychiatry, 20: 916-930
[3] Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, et al. (1990). Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science, 247: 1446-1451
[4] Maisonpierre PC, Le Beau MM, Espinosa R3rd, Ip NY, Belluscio L, de la Monte SM, et al. (1991). Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations. Genomics, 10: 558-568
[5] Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK (2013). GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther, 138: 155-175
[6] Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, Seidah NG, et al. (2001). Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. J Biol Chem, 276: 12660-12666
[7] Hock C, Heese K, Hulette C, Rosenberg C, Otten U (2000). Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol, 57: 846-851
[8] Allen SJ, Wilcock GK, Dawbarn D (1999). Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer’s disease. Biochem Biophys Res Commun, 264: 648-651
[9] Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1991). BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron, 7: 695-702
[10] Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, et al. (1999). Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett, 270: 45-48
[11] Ferrer I, Goutan E, Marin C, Rey MJ, Ribalta T (2000). Brain-derived neurotrophic factor in Huntington disease. Brain Res, 866: 257-261
[12] Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, et al. (2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry, 54: 70-75
[13] Bliss TV, Collingridge GL (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 361: 31-39
[14] Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B (1996). Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature, 381: 706-709
[15] Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995). Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A, 92: 8856-8860
[16] Liepinsh E, Ilag LL, Otting G, Ibanez CF (1997). NMR structure of the death domain of the p75 neurotrophin receptor. EMBO J, 16: 4999-5005
[17] Bartkowska K, Turlejski K, Djavadian RL (2010). Neurotrophins and their receptors in early development of the mammalian nervous system. Acta Neurobiol Exp (Wars), 70: 454-467
[18] Knusel B, Beck KD, Winslow JW, Rosenthal A, Burton LE, Widmer HR, et al. (1992). Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci, 12: 4391-4402
[19] Chen H, Weber AJ (2001). BDNF enhances retinal ganglion cell survival in cats with optic nerve damage. Invest Ophthalmol Vis Sci, 42: 966-974
[20] Scharfman HE, Goodman JH, Sollas AL, Croll SD (2002). Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor. Exp Neurol, 174: 201-214
[21] Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T (2007). Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics, 90: 397-406
[22] Baj G, Tongiorgi E (2009). BDNF splice variants from the second promoter cluster support cell survival of differentiated neuroblastoma upon cytotoxic stress. J Cell Sci, 122: 36-43
[23] Cerasa A, Tongiorgi E, Fera F, Gioia MC, Valentino P, Liguori M, et al. (2010). The effects of BDNF Val66Met polymorphism on brain function in controls and patients with multiple sclerosis: an imaging genetic study. Behav Brain Res, 207: 377-386
[24] Bian JT, Zhang JW, Zhang ZX, Zhao HL (2005). Association analysis of brain-derived neurotrophic factor (BDNF) gene 196 A/G polymorphism with Alzheimer’s disease (AD) in mainland Chinese. Neurosci Lett, 387: 11-16
[25] Sheikh HI, Hayden EP, Kryski KR, Smith HJ, Singh SM (2010). Genotyping the BDNF rs6265 (val66met) polymorphism by one-step amplified refractory mutation system PCR. Psychiatr Genet, 20: 109-112
[26] Parsian A, Sinha R, Racette B, Zhao JH, Perlmutter JS (2004). Association of a variation in the promoter region of the brain-derived neurotrophic factor gene with familial Parkinson’s disease. Parkinsonism Relat Disord, 10: 213-219
[27] Tsuchihashi Z, Dracopoli NC (2002). Progress in high throughput SNP genotyping methods. Pharmacogenomics J, 2: 103-110
[28] Landegren U, Nilsson M, Kwok PY (1998). Reading bits of genetic information: methods for single-nucleotide polymorphism analysis. Genome Res, 8: 769-776
[29] Kwok PY (2001). Methods for genotyping single nucleotide polymorphisms. Annu Rev Genomics Hum Genet, 2: 235-258
[30] Terrazzino S, Cargnin S, Viana M, Sances G, Tassorelli C (2017). Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism Impacts on Migraine Susceptibility: A Meta-analysis of Case-Control Studies. Front Neurol, 8: 159
[31] Bath KG, Lee FS (2006). Variant BDNF (Val66Met) impact on brain structure and function. Cogn Affect Behav Neurosci, 6: 79-85
[32] Petryshen TL, Sabeti PC, Aldinger KA, Fry B, Fan JB, Schaffner SF, et al. (2010). Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol Psychiatry, 15: 810-815
[33] Pivac N, Kim B, Nedic G, Joo YH, Kozaric-Kovacic D, Hong JP, et al. (2009). Ethnic differences in brain-derived neurotrophic factor Val66Met polymorphism in Croatian and Korean healthy participants. Croat Med J, 50: 43-48
[34] Zhang H, Ozbay F, Lappalainen J, Kranzler HR, van Dyck CH, Charney DS, et al. (2006). Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer’s disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence. Am J Med Genet B Neuropsychiatr Genet, 141B: 387-393
[35] Ventriglia M, Bocchio Chiavetto L, Benussi L, Binetti G, Zanetti O, Riva MA, et al. (2002). Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer’s disease. Mol Psychiatry, 7: 136-137
[36] Shimizu E, Hashimoto K, Iyo M (2004). Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am J Med Genet B Neuropsychiatr Genet, 126B: 122-123
[37] Olin D, MacMurray J, Comings DE (2005). Risk of late-onset Alzheimer’s disease associated with BDNF C270T polymorphism. Neurosci Lett, 381: 275-278
[38] Mirowska-Guzel D, Mach A, Gromadzka G, Czlonkowski A, Czlonkowska A (2008). BDNF A196G and C270T gene polymorphisms and susceptibility to multiple sclerosis in the Polish population. Gender differences. J Neuroimmunol, 193: 170-172
[39] Weinstock-Guttman B, Benedict RH, Tamano-Blanco M, Ramasamy DP, Stosic M, Polito J, et al. (2011). The rs2030324 SNP of brain-derived neurotrophic factor (BDNF) is associated with visual cognitive processing in multiple sclerosis. Pathophysiology, 18: 43-52
[40] Bodner SM, Berrettini W, van Deerlin V, Bennett DA, Wilson RS, Trojanowski JQ, et al. (2005). Genetic variation in the brain derived neurotrophic factor gene in Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet, 134B: 1-5
[41] Fukumoto N, Fujii T, Combarros O, Kamboh MI, Tsai SJ, Matsushita S, et al. (2010). Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer’s disease: New data and meta-analysis. Am J Med Genet B Neuropsychiatr Genet, 153B: 235-242
[42] Vepsalainen S, Castren E, Helisalmi S, Iivonen S, Mannermaa A, Lehtovirta M, et al. (2005). Genetic analysis of BDNF and TrkB gene polymorphisms in Alzheimer’s disease. J Neurol, 252: 423-428
[43] Matsushita S, Arai H, Matsui T, Yuzuriha T, Urakami K, Masaki T, et al. (2005). Brain-derived neurotrophic factor gene polymorphisms and Alzheimer’s disease. J Neural Transm (Vienna), 112: 703-711
[44] Mero IL, Smestad C, Lie BA, Lorentzen AR, Sandvik L, Landro NI, et al. (2012). Polymorphisms of the BDNF gene show neither association with multiple sclerosis susceptibility nor clinical course. J Neuroimmunol, 244: 107-110
[45] Reichardt LF (2006). Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci, 361: 1545-1564
[46] Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, et al. (2006). Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science, 314: 140-143
[47] Lang UE, Hellweg R, Sander T, Gallinat J (2009). The Met allele of the BDNF Val66Met polymorphism is associated with increased BDNF serum concentrations. Mol Psychiatry, 14: 120-122
[48] Minelli A, Zanardini R, Bonvicini C, Sartori R, Pedrini L, Gennarelli M, et al. (2011). BDNF serum levels, but not BDNF Val66Met genotype, are correlated with personality traits in healthy subjects. Eur Arch Psychiatry Clin Neurosci, 261: 323-329
[49] Ozan E, Okur H, Eker C, Eker OD, Gonul AS, Akarsu N (2010). The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels. Brain Res Bull, 81: 61-65
[50] Zhou Z, Lu T, Xu G, Yue X, Zhu W, Ma M, et al. (2011). Decreased serum brain-derived neurotrophic factor (BDNF) is associated with post-stroke depression but not with BDNF gene Val66Met polymorphism. Clin Chem Lab Med, 49: 185-189
[51] Yoshimura R, Kishi T, Suzuki A, Umene-Nakano W, Ikenouchi-Sugita A, Hori H, et al. (2011). The brain-derived neurotrophic factor (BDNF) polymorphism Val66Met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients. Prog Neuropsychopharmacol Biol Psychiatry, 35: 1022-1025
[52] Bus BA, Arias-Vasquez A, Franke B, Prickaerts J, de Graaf J, Voshaar RC (2012). Increase in serum brain-derived neurotrophic factor in met allele carriers of the BDNF Val66Met polymorphism is specific to males. Neuropsychobiology, 65: 183-187
[53] Pezawas L, Verchinski BA, Mattay VS, Callicott JH, Kolachana BS, Straub RE, et al. (2004). The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci, 24: 10099-10102
[54] Erickson KI, Kim JS, Suever BL, Voss MW, Francis BM, Kramer AF (2008). Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms. Front Hum Neurosci, 2: 11
[55] Harris SE, Fox H, Wright AF, Hayward C, Starr JM, Whalley LJ, et al. (2006). The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills. Mol Psychiatry, 11: 505-513
[56] Hashimoto T, Fukui K, Takeuchi H, Yokota S, Kikuchi Y, Tomita H, et al. (2016). Effects of the BDNF Val66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents. Cereb Cortex, 26: 1795-1803
[57] Quigley HA (1993). Open-angle glaucoma. N Engl J Med, 328: 1097-1106
[58] Harwerth RS, Wheat JL, Fredette MJ, Anderson DR (2010). Linking structure and function in glaucoma. Prog Retin Eye Res, 29: 249-271
[59] Quigley HA, Broman AT (2006). The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 90: 262-267
[60] Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, Sunden SL, et al. (1997). Identification of a gene that causes primary open angle glaucoma. Science, 275: 668-670
[61] Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, et al. (2002). Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science, 295: 1077-1079
[62] Ramdas WD, van Koolwijk LM, Lemij HG, Pasutto F, Cree AJ, Thorleifsson G, et al. (2011). Common genetic variants associated with open-angle glaucoma. Hum Mol Genet, 20: 2464-2471
[63] Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al. (2012). Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma. Nat Genet, 44: 1142-1146
[64] Perez MT, Caminos E (1995). Expression of brain-derived neurotrophic factor and of its functional receptor in neonatal and adult rat retina. Neurosci Lett, 183: 96-99
[65] Cellerino A, Kohler K (1997). Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergic amacrine cells in the vertebrate retina. J Comp Neurol, 386: 149-160
[66] Pease ME, McKinnon SJ, Quigley HA, Kerrigan-Baumrind LA, Zack DJ (2000). Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci, 41: 764-774
[67] Mansour-Robaey S, Clarke DB, Wang YC, Bray GM, Aguayo AJ (1994). Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A, 91: 1632-1636
[68] Ko ML, Hu DN, Ritch R, Sharma SC, Chen CF (2001). Patterns of retinal ganglion cell survival after brain-derived neurotrophic factor administration in hypertensive eyes of rats. Neurosci Lett, 305: 139-142
[69] Gupta V, You Y, Li J, Gupta V, Golzan M, Klistorner A, et al. (2014). BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma. Biochim Biophys Acta, 1842: 1567-1578
[70] Domenici L, Origlia N, Falsini B, Cerri E, Barloscio D, Fabiani C, et al. (2014). Rescue of retinal function by BDNF in a mouse model of glaucoma. PLoS One, 9: e115579
[71] Martin KR, Quigley HA, Zack DJ, Levkovitch-Verbin H, Kielczewski J, Valenta D, et al. (2003). Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. Invest Ophthalmol Vis Sci, 44: 4357-4365
[72] Nowak A, Szaflik JP, Gacek M, Przybylowska-Sygut K, Kaminska A, Szaflik J, et al. (2014). BDNF and HSP gene polymorphisms and their influence on the progression of primary open-angle glaucoma in a Polish population. Arch Med Sci, 10: 1206-1213
[73] Calabresi PA (2004). Diagnosis and management of multiple sclerosis. Am Fam Physician, 70: 1935-1944
[74] Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. (2014). Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology, 83: 1022-1024
[75] Organization WH (2008). Atlas. Multiple sclerosis resources in the world 2008. Atlas Multiple Sclerosis Resources in the World, 98: 103-122
[76] International Multiple Sclerosis Genetics C, Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, et al. (2007). Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med, 357: 851-862
[77] Australia, New Zealand Multiple Sclerosis Genetics C (2009). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet, 41: 824-828
[78] Jensen CJ, Stankovich J, Van der Walt A, Bahlo M, Taylor BV, van der Mei IA, et al. (2010). Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients. PLoS One, 5: e10003
[79] Liguori M, Fera F, Patitucci A, Manna I, Condino F, Valentino P, et al. (2009). A longitudinal observation of brain-derived neurotrophic factor mRNA levels in patients with relapsing-remitting multiple sclerosis. Brain Res, 1256: 123-128
[80] Liguori M, Fera F, Gioia MC, Valentino P, Manna I, Condino F, et al. (2007). Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis. Genes Brain Behav, 6: 177-183
[81] Ramasamy DP, Ramanathan M, Cox JL, Antulov R, Weinstock-Guttman B, Bergsland N, et al. (2011). Effect of Met66 allele of the BDNF rs6265 SNP on regional gray matter volumes in patients with multiple sclerosis: A voxel-based morphometry study. Pathophysiology, 18: 53-60
[82] Zivadinov R, Weinstock-Guttman B, Benedict R, Tamano-Blanco M, Hussein S, Abdelrahman N, et al. (2007). Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor. Hum Mol Genet, 16: 2659-2668
[83] Dinacci D, Tessitore A, Russo A, De Bonis ML, Lavorgna L, Picconi O, et al. (2011). BDNF Val66Met polymorphism and brain volumes in multiple sclerosis. Neurol Sci, 32: 117-123
[84] Fera F, Passamonti L, Cerasa A, Gioia MC, Liguori M, Manna I, et al. (2013). The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls. PLoS One, 8: e61063
[85] Santoro M, Nociti V, De Fino C, Caprara A, Giordano R, Palomba N, et al. (2016). Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception. Eur J Neurol, 23: 630-640
[86] Lindquist S, Schott BH, Ban M, Compston DA, Sawcer S, Sailer M (2005). The BDNF-Val66Met polymorphism: implications for susceptibility to multiple sclerosis and severity of disease. J Neuroimmunol, 167: 183-185
[87] Blanco Y, Gomez-Choco M, Arostegui JL, Casanova B, Martinez-Rodriguez JE, Bosca I, et al. (2006). No association of the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) to multiple sclerosis. Neurosci Lett, 396: 217-219
[88] Sadovnick AD, Ebers GC (1993). Epidemiology of multiple sclerosis: a critical overview. Can J Neurol Sci, 20: 17-29
[89] Rosati G (2001). The prevalence of multiple sclerosis in the world: an update. Neurol Sci, 22: 117-139
[90] Kira J (2003). Multiple sclerosis in the Japanese population. Lancet Neurol, 2: 117-127
[91] Cabre P, Signate A, Olindo S, Merle H, Caparros-Lefebvre D, Bera O, et al. (2005). Role of return migration in the emergence of multiple sclerosis in the French West Indies. Brain, 128: 2899-2910
[92] Cossburn M, Tackley G, Baker K, Ingram G, Burtonwood M, Malik G, et al. (2012). The prevalence of neuromyelitis optica in South East Wales. Eur J Neurol, 19: 655-659
[93] Mattson MP (2004). Pathways towards and away from Alzheimer’s disease. Nature, 430: 631-639
[94] Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement, 3: 186-191
[95] Herrmann N, Chau SA, Kircanski I, Lanctot KL (2011). Current and emerging drug treatment options for Alzheimer’s disease: a systematic review. Drugs, 71: 2031-2065
[96] Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 349: 704-706
[97] Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, et al. (1995). Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature, 376: 775-778
[98] Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, et al. (1995). Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science, 269: 973-977
[99] Selkoe DJ (2001). Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev, 81: 741-766
[100] Lim YY, Villemagne VL, Laws SM, Ames D, Pietrzak RH, Ellis KA, et al. (2014). Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer’s disease: a preliminary study. PLoS One, 9: e86498
[101] Lim YY, Villemagne VL, Laws SM, Ames D, Pietrzak RH, Ellis KA, et al. (2013). BDNF Val66Met, Abeta amyloid, and cognitive decline in preclinical Alzheimer’s disease. Neurobiol Aging, 34: 2457-2464
[102] Lim YY, Hassenstab J, Cruchaga C, Goate A, Fagan AM, Benzinger TL, et al. (2016). BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease. Brain, 139: 2766-2777
[103] Nishimura M, Kuno S, Kaji R, Kawakami H (2005). Brain-derived neurotrophic factor gene polymorphisms in Japanese patients with sporadic Alzheimer’s disease, Parkinson’s disease, and multiple system atrophy. Mov Disord, 20: 1031-1033
[104] Tsai SJ, Hong CJ, Liu HC, Liu TY, Hsu LE, Lin CH (2004). Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms with Alzheimer’s disease and age of onset. Neuropsychobiology, 49: 10-12
[105] Combarros O, Infante J, Llorca J, Berciano J (2004). Polymorphism at codon 66 of the brain-derived neurotrophic factor gene is not associated with sporadic Alzheimer’s disease. Dement Geriatr Cogn Disord, 18: 55-58
[106] Bagnoli S, Nacmias B, Tedde A, Guarnieri BM, Cellini E, Petruzzi C, et al. (2004). Brain-derived neurotrophic factor genetic variants are not susceptibility factors to Alzheimer’s disease in Italy. Ann Neurol, 55: 447-448
[107] Lee J, Fukumoto H, Orne J, Klucken J, Raju S, Vanderburg CR, et al. (2005). Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms. Exp Neurol, 194: 91-96
[108] Kunugi H, Ueki A, Otsuka M, Isse K, Hirasawa H, Kato N, et al. (2001). A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer’s disease. Mol Psychiatry, 6: 83-86
[109] Foltynie T, Lewis SG, Goldberg TE, Blackwell AD, Kolachana BS, Weinberger DR, et al. (2005). The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease. J Neurol, 252: 833-838
[110] Warner TT, Schapira AH (2003). Genetic and environmental factors in the cause of Parkinson’s disease. Ann Neurol, 53 Suppl 3: S16-23; discussion S23-15
[111] Howells DW, Porritt MJ, Wong JY, Batchelor PE, Kalnins R, Hughes AJ, et al. (2000). Reduced BDNF mRNA expression in the Parkinson’s disease substantia nigra. Exp Neurol, 166: 127-135
[112] Scalzo P, Kummer A, Bretas TL, Cardoso F, Teixeira AL (2010). Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson’s disease. J Neurol, 257: 540-545
[113] Momose Y, Murata M, Kobayashi K, Tachikawa M, Nakabayashi Y, Kanazawa I, et al. (2002). Association studies of multiple candidate genes for Parkinson’s disease using single nucleotide polymorphisms. Annals of neurology, 51: 133-136
[114] Karamohamed S, Latourelle JC, Racette BA, Perlmutter JS, Wooten GF, Lew M, et al. (2005). BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study. Neurology, 65: 1823-1825
[115] Guerini FR BE, Riboldazzi G, Zangaglia R, Pianezzola C, Bono G, et al. (2009). BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease. European Journal of Neurology, 16: 1240-1245
[116] Altmann V, Schumacher-Schuh AF, Rieck M, Callegari-Jacques SM, Rieder CR, Hutz MH (2016). Val66Met BDNF polymorphism is associated with Parkinson’s disease cognitive impairment. Neurosci Lett, 615: 88-91
[117] Foltynie T, Cheeran B, Williams-Gray CH, Edwards MJ, Schneider SA, Weinberger D, et al. (2009). BDNF val66met influences time to onset of levodopa induced dyskinesia in Parkinson’s disease. J Neurol Neurosurg Psychiatry, 80: 141-144
[118] van der Kolk NM, Speelman AD, van Nimwegen M, Kessels RP, IntHout J, Hakobjan M, et al. (2015). BDNF polymorphism associates with decline in set shifting in Parkinson’s disease. Neurobiol Aging, 36: 1605 e1601-1606
[119] Saarela MS, Lehtimaki T, Rinne JO, Huhtala H, Rontu R, Hervonen A, et al. (2006). No association between the brain-derived neurotrophic factor 196 G>A or 270 C>T polymorphisms and Alzheimer’s or Parkinson’s disease. Folia Neuropathol, 44: 12-16
[120] Hakansson A, Melke J, Westberg L, Shahabi HN, Buervenich S, Carmine A, et al. (2003). Lack of association between the BDNF Val66Met polymorphism and Parkinson’s disease in a Swedish population. Ann Neurol, 53: 823
[121] Hong CJ, Liu HC, Liu TY, Lin CH, Cheng CY, Tsai SJ (2003). Brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in Parkinson’s disease and age of onset. Neurosci Lett, 353: 75-77
[122] Chen CM, Chen IC, Chang KH, Chen YC, Lyu RK, Liu YT, et al. (2007). Nuclear receptor NR4A2 IVS6 +18insG and brain derived neurotrophic factor (BDNF) V66M polymorphisms and risk of Taiwanese Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet, 144B: 458-462
[123] Xiromerisiou G, Hadjigeorgiou GM, Eerola J, Fernandez HH, Tsimourtou V, Mandel R, et al. (2007). BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson’s disease in diverse ethnic groups. Neurosci Lett, 415: 59-63
[124] Karakasis C, Kalinderi K, Katsarou Z, Fidani L, Bostantjopoulou S (2011). Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with Parkinson’s disease in a Greek population. J Clin Neurosci, 18: 1744-1745
[125] Bialecka M, Kurzawski M, Roszmann A, Robowski P, Sitek EJ, Honczarenko K, et al. (2014). BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson’s disease. Neurosci Lett, 561: 86-90
[126] Gao L, Diaz-Corrales FJ, Carrillo F, Diaz-Martin J, Caceres-Redondo MT, Carballo M, et al. (2010). Brain-derived neurotrophic factor G196A polymorphism and clinical features in Parkinson’s disease. Acta Neurol Scand, 122: 41-45
[127] Hwang JP, Tsai SJ, Hong CJ, Yang CH, Lirng JF, Yang YM (2006). The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression. Neurobiol Aging, 27: 1834-1837
[128] Getzmann S, Gajewski PD, Hengstler JG, Falkenstein M, Beste C (2013). BDNF Val66Met polymorphism and goal-directed behavior in healthy elderly - evidence from auditory distraction. Neuroimage, 64: 290-298
[129] Gajewski PD, Hengstler JG, Golka K, Falkenstein M, Beste C (2012). The Met-genotype of the BDNF Val66Met polymorphism is associated with reduced Stroop interference in elderly. Neuropsychologia, 50: 3554-3563
[130] Miyajima F, Ollier W, Mayes A, Jackson A, Thacker N, Rabbitt P, et al. (2008). Brain-derived neurotrophic factor polymorphism Val66Met influences cognitive abilities in the elderly. Genes Brain Behav, 7: 411-417
[131] Voineskos AN, Lerch JP, Felsky D, Shaikh S, Rajji TK, Miranda D, et al. (2011). The brain-derived neurotrophic factor Val66Met polymorphism and prediction of neural risk for Alzheimer disease. Arch Gen Psychiatry, 68: 198-206
[132] Videbech P, Ravnkilde B (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry, 161: 1957-1966
[133] Bueller JA, Aftab M, Sen S, Gomez-Hassan D, Burmeister M, Zubieta JK (2006). BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biol Psychiatry, 59: 812-815
[134] Takahashi T, Suzuki M, Tsunoda M, Kawamura Y, Takahashi N, Maeno N, et al. (2008). The association of genotypic combination of the DRD3 and BDNF polymorphisms on the adhesio interthalamica and medial temporal lobe structures. Prog Neuropsychopharmacol Biol Psychiatry, 32: 1236-1242
[135] Wang C, Zhang Y, Liu B, Long H, Yu C, Jiang T (2014). Dosage effects of BDNF Val66Met polymorphism on cortical surface area and functional connectivity. J Neurosci, 34: 2645-2651
[1] Xue Yingnan, Zhang Zhenhua, Wen Caiyun, Liu Huiru, Wang Suyuan, Li Jiance, Zhuge Qichuan, Chen Weijian, Ye Qiong. Characterization of Alzheimer’s Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging[J]. Aging and disease, 2019, 10(5): 1026-1036.
[2] Zhou Xiao-Li, Xu Meng-Bei, Jin Ting-Yu, Rong Pei-Qing, Zheng Guo-Qing, Lin Yan. Preclinical Evidence and Possible Mechanisms of Extracts or Compounds from Cistanches for Alzheimer’s Disease[J]. Aging and disease, 2019, 10(5): 1075-1093.
[3] Zhi-Ying Tian, Chun-Yan Wang, Tao Wang, Yan-Chun Li, Zhan-You Wang. Glial S100A6 Degrades β-amyloid Aggregation through Targeting Competition with Zinc Ions[J]. Aging and disease, 2019, 10(4): 756-769.
[4] Takehiko Yamanaka, Yuto Uchida, Keita Sakurai, Daisuke Kato, Masayuki Mizuno, Toyohiro Sato, Yuta Madokoro, Yuko Kondo, Ayuko Suzuki, Yoshino Ueki, Fumiyasu Ishii, Cesar V Borlongan, Noriyuki Matsukawa. Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions[J]. Aging and disease, 2019, 10(4): 711-718.
[5] Yu-Sheng Li, Zhi-Hua Yang, Yao Zhang, Jing Yang, Dan-Dan Shang, Shu-Yu Zhang, Jun Wu, Yan Ji, Lu Zhao, Chang-He Shi, Yu-Ming Xu. Two Novel Mutations and a de novo Mutation in PSEN1 in Early-onset Alzheimer’s Disease[J]. Aging and disease, 2019, 10(4): 908-914.
[6] Qing-Qing Tao, Yu-Chao Chen, Zhi-Ying Wu. The role of CD2AP in the Pathogenesis of Alzheimer's Disease[J]. Aging and disease, 2019, 10(4): 901-907.
[7] Rongrong Han, Zeyue Liu, Nannan Sun, Shu Liu, Lanlan Li, Yan Shen, Jianbo Xiu, Qi Xu. BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1/RAGE/NF-κB Pathway[J]. Aging and disease, 2019, 10(3): 611-625.
[8] Kunyu Li, Jiatong Li, Jialin Zheng, Song Qin. Reactive Astrocytes in Neurodegenerative Diseases[J]. Aging and disease, 2019, 10(3): 664-675.
[9] Christopher Bi, Stephanie Bi, Bin Li. Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 383-403.
[10] Seong Gak Jeon, Eun Ji Song, Dongje Lee, Junyong Park, Yunkwon Nam, Jin-il Kim, Minho Moon. Traditional Oriental Medicines and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 307-328.
[11] Ashok K. Shetty, Raghavendra Upadhya, Leelavathi N. Madhu, Maheedhar Kodali. Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 470-482.
[12] Jong Bin Bae,Ji Won Han,Kyung Phil Kwak,Bong Jo Kim,Shin Gyeom Kim,Jeong Lan Kim,Tae Hui Kim,Seung-Ho Ryu,Seok Woo Moon,Joon Hyuk Park,Jong Chul Youn,Dong Young Lee,Dong Woo Lee,Seok Bum Lee,Jung Jae Lee,Jin Hyeong Jhoo,Ki Woong Kim. Is Dementia More Fatal Than Previously Estimated? A Population-based Prospective Cohort Study[J]. Aging and disease, 2019, 10(1): 1-11.
[13] Wei Zhuang,Lifeng Yue,Xiaofang Dang,Fei Chen,Yuewen Gong,Xiaolan Lin,Yumin Luo. Rosenroot (Rhodiola): Potential Applications in Aging-related Diseases[J]. Aging and disease, 2019, 10(1): 134-146.
[14] Antonina Luca, Carmela Calandra, Maria Luca. Molecular Bases of Alzheimer’s Disease and Neurodegeneration: The Role of Neuroglia[J]. Aging and disease, 2018, 9(6): 1134-1152.
[15] Manuel Scimeca, Federica Centofanti, Monica Celi, Elena Gasbarra, Giuseppe Novelli, Annalisa Botta, Umberto Tarantino. Vitamin D Receptor in Muscle Atrophy of Elderly Patients: A Key Element of Osteoporosis-Sarcopenia Connection[J]. Aging and disease, 2018, 9(6): 952-964.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd