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Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults

Published online by Cambridge University Press:  24 June 2014

Christos Sidiropoulos*
Affiliation:
Department of Neurology, Henry Ford Hospital, Detroit, MI, USA Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität, Erlangen, Germany
Kourosh Jafari-Khouzani
Affiliation:
Department of Diagnostic Radiology, Henry Ford Hospital, Detroit, MI, USA
Hamid Soltanian-Zadeh
Affiliation:
Department of Diagnostic Radiology, Henry Ford Hospital, Detroit, MI, USA
Panayiotis Mitsias
Affiliation:
Department of Neurology, Henry Ford Hospital, Detroit, MI, USA
Panagiotis Alexopoulos
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität, Erlangen, Germany Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany
Tanja Richter-Schmidinger
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität, Erlangen, Germany
Martin Reichel
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität, Erlangen, Germany
Piotr Lewczuk
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität, Erlangen, Germany
Arnd Doerfler
Affiliation:
Department of Neuroradiology, Friedrich-Alexander Universität, Erlangen, Germany
Johannes Kornhuber
Affiliation:
Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität, Erlangen, Germany
*Corresponding
Christos Sidiropoulos, Henry Ford Hospital, Department of Neurology, 2799 West Grand Blvd, Detroit, Michigan 48202, USA. Tel: +1 313 916 7957; Fax: +1 313 916 8038; E-mail: csidiro1@hfhs.org

Extract

Objective: Brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) are thought to be implicated in a variety of neuronal processes, including cell growth, resilience to noxious stimuli and synaptic plasticity. A Val to Met substitution at codon 66 in the BDNF protein has been associated with a variety of neuropsychiatric conditions. The ApoE4 allele is considered a risk factor for late-onset Alzheimer's disease, but its effects on young adults are less clear. We sought to investigate the effects of those two polymorphisms on hemispheric and lateral ventricular volumes of young healthy adults.

Methods: Hemispheric and lateral ventricular volumes of 144 healthy individuals, aged 19–35 years, were measured using high resolution magnetic resonance imaging and data were correlated with BDNF and ApoE genotypes.

Results: There were no correlations between BDNF or ApoE genotype and hemispheric or lateral ventricular volumes.

Conclusion: These findings indicate that it is unlikely that either the BDNF Val66Met or ApoE polymorphisms exert any significant effect on hemispheric or lateral ventricular volume. However, confounding epistatic genetic effects as well as relative insensitivity of the volumetric methods used cannot be ruled out. Further imaging analyses are warranted to better define any genetic influence of the BDNF Val6Met and ApoE polymorphism on brain structure of young healthy adults.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2011

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References

1.Hofer, M, Pagliusi, SR, Hohn, A, Leibrock, J, Barde, YA.Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J 1990;9: 24592464.Google ScholarPubMed
2.Baquet, ZC, Bickford, PC, Jones, KR.Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 2005;25:62516259.CrossRefGoogle ScholarPubMed
3.Gorski, JA, Zeiler, SR, Tamowski, S, Jones, KR.Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. J Neurosci 2003;23:68566865.CrossRefGoogle ScholarPubMed
4.Morse, JK, Wiegand, SJ, Anderson, K et al. Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J Neurosci 1993;13:41464156.CrossRefGoogle ScholarPubMed
5.Lipsky, RH, Marini, AM.Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Ann N Y Acad Sci 2007;1122:130143.CrossRefGoogle ScholarPubMed
6.Tian, F, Marini, AM, Lipsky, RH.NMDA receptor activation induces differential epigenetic modification of BDNF promoters in hippocampal neurons. Amino Acids 2009.Google ScholarPubMed
7.Chen, ZY, Patel, PD, Sant, G, Meng, CX, Teng, KK, Hempstead, BL, Lee, FS.Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 2004; 24:44014411.CrossRefGoogle ScholarPubMed
8.Egan, MF, Kojima, M, Callicott, JH et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003;112:257269.CrossRefGoogle ScholarPubMed
9.Sen, S, Nesse, RM, Stoltenberg, SF et al. A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 2003;28:397401.CrossRefGoogle Scholar
10.Sklar, P, Gabriel, SB, McInnis, MG et al. Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry 2002;7:579593.CrossRefGoogle ScholarPubMed
11.Pezawas, L, Verchinski, BA, Mattay, VS et al. The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 2004; 24:1009910102.CrossRefGoogle ScholarPubMed
12.Hariri, AR, Goldberg, TE, Mattay, VS, Kolachana, BS, Callicott, JH, Egan, MF, Weinberger, DR.Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci 2003;23:66906694.CrossRefGoogle ScholarPubMed
13.Neves-Pereira, M, Mundo, E, Muglia, P, King, N, Macciardi, F, Kennedy, JL.The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. Am J Hum Genet 2002;71:651655.CrossRefGoogle ScholarPubMed
14.Agartz, I, Sedvall, GC, Terenius, L, Kulle, B, Frigessi, A, Hall, H, Jonsson, EG.BDNF gene variants and brain morphology in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2006;141B:513523.CrossRefGoogle Scholar
15.Bueller, JA, Aftab, M, Sen, S, Gomez-Hassan, D, Burmeister, M, Zubieta, JK.BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biol Psychiatry 2006;59:812815.CrossRefGoogle ScholarPubMed
16.Szeszko, PR, Lipsky, R, Mentschel, C et al. Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry 2005;10: 631636.CrossRefGoogle ScholarPubMed
17.Frodl, T, Schule, C, Schmitt, G et al. Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry 2007;64:410416.CrossRefGoogle ScholarPubMed
18.Nemoto, K, Ohnishi, T, Mori, T, Moriguchi, Y, Hashimoto, R, Asada, T, Kunugi, H.The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology. Neurosci Lett 2006; 397:2529.CrossRefGoogle ScholarPubMed
19.Toro, R, Chupin, M, Garnero, L et al. Brain volumes and Val66Met polymorphism of the BDNF gene: local or global effects?. Brain Struct Funct 2009;213:501509.CrossRefGoogle ScholarPubMed
20.Gerdes, LU, Gerdes, C, Hansen, PS, Klausen, IC, Faergeman, O, Dyerberg, J.The apolipoprotein E polymorphism in Greenland Inuit in its global perspective. Hum Genet 1996;98:546550.CrossRefGoogle ScholarPubMed
21.Gerdes, LU, Klausen, IC, Sihm, I, Faergeman, O.Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genet Epidemiol 1992;9:155167.CrossRefGoogle Scholar
22.Corbo, RM, Scacchi, R.Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty' allele? Ann Hum Genet 1999;63:301310.CrossRefGoogle ScholarPubMed
23.Beffert, U, Nematollah Farsian, F, Masiulis, I, Hammer, RE, Yoon, SO, Giehl, KM, Herz, J.ApoE receptor 2 controls neuronal survival in the adult brain. Curr Biol 2006; 16:24462452.CrossRefGoogle ScholarPubMed
24.Beffert, U, Stolt, PC, Herz, J.Functions of lipoprotein receptors in neurons. J Lipid Res 2004;45:403409.CrossRefGoogle ScholarPubMed
25.Dong, LM, Weisgraber, KH.Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins. J Biol Chem 1996;271:1905319057.CrossRefGoogle ScholarPubMed
26.Morrow, JA, Hatters, DM, Lu, B, Hochtl, P, Oberg, KA, Rupp, B, Weisgraber, KH.Apolipoprotein E4 forms a molten globule. A potential basis for its association with disease. J Biol Chem 2002;277:5038050385.CrossRefGoogle ScholarPubMed
27.Jiang, Q, Lee, CY, Mandrekar, S et al. ApoE promotes the proteolytic degradation of Abeta. Neuron 2008;58: 681693.CrossRefGoogle ScholarPubMed
28.Burggren, AC, Zeineh, MM, Ekstrom, AD, Braskie, MN, Thompson, PM, Small, GW, Bookheimer, SY.Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers. Neuroimage 2008;41:11771183.CrossRefGoogle ScholarPubMed
29.Jak, AJ, Houston, WS, Nagel, BJ, Corey-Bloom, J, Bondi, MW.Differential cross-sectional and longitudinal impact of APOE genotype on hippocampal volumes in nondemented older adults. Dement Geriatr Cogn Disord 2007;23: 382389.CrossRefGoogle ScholarPubMed
30.Lind, J, Larsson, A, Persson, J et al. Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory. Neurosci Lett 2006;396:2327.CrossRefGoogle ScholarPubMed
31.Soininen, H, Partanen, K, Pitkanen, A et al. Decreased hippocampal volume asymmetry on MRIs in nondemented elderly subjects carrying the apolipoprotein E epsilon 4 allele. Neurology 1995;45:391392.CrossRefGoogle ScholarPubMed
32.Tohgi, H, Takahashi, S, Kato, E et al. Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E epsilon4 allele. Neurosci Lett 1997;236:2124.CrossRefGoogle ScholarPubMed
33.Wishart, HA, Saykin, AJ, McAllister, TW et al. Regional brain atrophy in cognitively intact adults with a single APOE epsilon4 allele. Neurology 2006;67:12211224.CrossRefGoogle ScholarPubMed
34.Espeseth, T, Westlye, LT, Fjell, AM, Walhovd, KB, Rootwelt, H, Reinvang, I.Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E epsilon 4. Neurobiol Aging 2008;29:329340.CrossRefGoogle ScholarPubMed
35.Shaw, P, Lerch, JP, Pruessner, JC et al. Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurol 2007;6:494500.CrossRefGoogle Scholar
36.Mondadori, CR, de Quervain, DJ, Buchmann, A et al. Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. Cereb Cortex 2007;17:19341947.CrossRefGoogle ScholarPubMed
37.Bradley, KM, Bydder, GM, Budge, MM, Hajnal, JV, White, SJ, Ripley, BD, Smith, AD.Serial brain MRI at 3–6 month intervals as a surrogate marker for Alzheimer's disease. Br J Radiol 2002;75:506513.CrossRefGoogle ScholarPubMed
38.Carmichael, OT, Kuller, LH, Lopez, OL et al. Ventricular volume and dementia progression in the Cardiovascular Health Study. Neurobiol Aging 2007;28:389397.CrossRefGoogle ScholarPubMed
39.Jack, CR Jr, Shiung, MM, Gunter, JL et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology 2004;62:591600.CrossRefGoogle ScholarPubMed
40.Thompson, PM, Hayashi, KM, De Zubicaray, GI et al. Mapping hippocampal and ventricular change in Alzheimer disease. Neuroimage 2004;22:17541766.CrossRefGoogle ScholarPubMed
41.Wang, D, Chalk, JB, Rose, SE et al. MR image-based measurement of rates of change in volumes of brain structures. Part II: application to a study of Alzheimer's disease and normal aging. Magn Reson Imaging 2002;20:4148.CrossRefGoogle ScholarPubMed
42.Ferrarini, L, Palm, WM, Olofsen, H, van Buchem, MA, Reiber, JH, Admiraal-Behloul, F.Shape differences of the brain ventricles in Alzheimer's disease. Neuroimage 2006;32:10601069.CrossRefGoogle ScholarPubMed
43.Giesel, FL, Hahn, HK, Thomann, PA et al. Temporal horn index and volume of medial temporal lobe atrophy using a new semiautomated method for rapid and precise assessment. AJNR Am J Neuroradiol 2006;27:14541458.Google ScholarPubMed
44.Shen, D, Davatzikos, C.HAMMER: hierarchical attribute matching mechanism for elastic registration. IEEE Trans Med Imaging 2002;21:14211439.CrossRefGoogle ScholarPubMed
45.Smith, SM.Fast robust automated brain extraction. Hum Brain Mapp 2002;17:143155.CrossRefGoogle ScholarPubMed
46.Zhang, Y, Brady, M, Smith, S.Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 2001;20:4557.CrossRefGoogle ScholarPubMed
47.Rorden, C, Brett, M.Stereotaxic display of brain lesions. Behav Neurol 2000;12:191200.CrossRefGoogle ScholarPubMed
48.Richter-Schmidinger, T, Alexopoulos, P, Horn, M, Maus, S et al. Influence of Brain-derived neurotrophic factor and Apolipoprotein E genetic variants on hippocampal volume and memory performance in healthy young adults. J Neural Transm 2011;118:249257.CrossRefGoogle ScholarPubMed
49.Van Hoesen, GW, Parvizi, J, Chu, CC.Orbitofrontal cortex pathology in Alzheimer's disease. Cereb Cortex 2000;10: 243251.CrossRefGoogle ScholarPubMed
50.Ongur, D, Ferry, AT, Price, JL.Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol 2003;460:425449.CrossRefGoogle ScholarPubMed
51.Debette, S, Wolf, PA, Beiser, A et al. Association of parental dementia with cognitive and brain MRI measures in middle-aged adults. Neurology 2009;73:20712078.CrossRefGoogle ScholarPubMed
52.Scarmeas, N, Habeck, CG, Hilton, J, Anderson, KE, Flynn, J, Park, A, Stern, Y.APOE related alterations in cerebral activation even at college age. J Neurol Neurosurg Psychiatry 2005;76:14401444.CrossRefGoogle ScholarPubMed
53.Jack, CR Jr.Petersen, RC, Xu, YC et al. Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease. Ann Neurol 1998;43:303310.CrossRefGoogle ScholarPubMed
54.Reiman, EM, Uecker, A, Caselli, RJ et al. Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Ann Neurol 1998;44:288291.CrossRefGoogle ScholarPubMed
55.Schmidt, H, Schmidt, R, Fazekas, F, Semmler, J, Kapeller, P, Reinhart, B, Kostner, GM.Apolipoprotein E e4 allele in the normal elderly: neuropsychologic and brain MRI correlates. Clin Genet 1996;50:293299.CrossRefGoogle ScholarPubMed
56.Geuze, E, Vermetten, E, Bremner, JD.MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed. Mol Psychiatry 2005;10:147159.CrossRefGoogle ScholarPubMed
57.Miyajima, F, Quinn, JP, Horan, M, Pickles, A, Ollier, WE, Pendleton, N, Payton, A.Additive effect of BDNF and REST polymorphisms is associated with improved general cognitive ability. Genes Brain Behav 2008;7:714719.CrossRefGoogle ScholarPubMed
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Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults
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