Transcriptome meta-analysis reveals a central role for sex steroids in the degeneration of hippocampal neurons in Alzheimer's disease

BMC Systems Biology

Volumn 7, Issue , 2013, Pages

  Winkler, Jessica M ^a   Fox, Howard S ^a  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Androgen receptor; Estrogen receptor; Graph theory; Hippocampus; Neurodegeneration

Indexed keywords

STEROID;

ALZHEIMER DISEASE; ARTICLE; GENE EXPRESSION PROFILING; GENETICS; HIPPOCAMPUS; HUMAN; META ANALYSIS; METABOLISM; METHODOLOGY; NERVE CELL; PATHOLOGY; SYSTEMS BIOLOGY;

ALZHEIMER DISEASE; GENE EXPRESSION PROFILING; HIPPOCAMPUS; HUMANS; NEURONS; STEROIDS; SYSTEMS BIOLOGY;

EID: 84879437081     PISSN: None     EISSN: 17520509     Source Type: Journal    
DOI: 10.1186/1752-0509-7-51     Document Type: Article

References (97)

1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of alzheimer's disease. Alzheimers Dement 2007, 3(3):186-191. 10.1016/j.jalz.2007.04.381, 19595937.
2. Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B. Recommendations for the diagnosis and management of alzheimer's disease and other disorders associated with dementia: Efns guideline. Eur J Neurol 2007, 14(1):e1-e26. 10.1111/j.1468-1331.2006.01605.x, 18028183.
3. Spires-Jones T, Knafo S. Spines, plasticity, and cognition in alzheimer's model mice. Neural Plast 2012, 2012:319836. 3238410, 22203915.
4. Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM. Amyloid deposition precedes tangle formation in a triple transgenic model of alzheimer's disease. Neurobiol Aging 2003, 24(8):1063-1070. 10.1016/j.neurobiolaging.2003.08.012, 14643377.
5. Blalock EM, Buechel HM, Popovic J, Geddes JW, Landfield PW. Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient alzheimer's disease. J Chem Neuroanat 2011, 42(2):118-126. 10.1016/j.jchemneu.2011.06.007, 3163806, 21756998.
6. Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Walker DG, Caselli RJ, Kukull WA, McKeel D, Morris JC, Hulette C, Schmechel D, Alexander GE, Reiman EM, Rogers J, Stephan DA. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics 2007, 28(3):311-322. 2259385, 17077275.
7. Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A, Niedzielko TL, Schneider LE, Mastroeni D, Caselli R, Kukull W, Morris JC, Hulette CM, Schmechel D, Rogers J, Stephan DA. Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci USA 2008, 105(11):4441-4446. 10.1073/pnas.0709259105, 2393743, 18332434.
8. Xu PT, Li YJ, Qin XJ, Scherzer CR, Xu H, Schmechel DE, Hulette CM, Ervin J, Gullans SR, Haines J, Pericak-Vance MA, Gilbert JR. Differences in apolipoprotein e3/3 and e4/4 allele-specific gene expression in hippocampus in alzheimer disease. Neurobiol Dis 2006, 21(2):256-275. 10.1016/j.nbd.2005.07.004, 16198584.
9. Parachikova A, Agadjanyan MG, Cribbs DH, Blurton-Jones M, Perreau V, Rogers J, Beach TG, Cotman CW. Inflammatory changes parallel the early stages of alzheimer disease. Neurobiol Aging 2007, 28(12):1821-1833. 10.1016/j.neurobiolaging.2006.08.014, 2198930, 17052803.
10. Katsel P, Tan W, Haroutunian V. Gain in brain immunity in the oldest-old differentiates cognitively normal from demented individuals. PLoS One 2009, 4(10):e7642. 10.1371/journal.pone.0007642, 2764344, 19865478.
11. Haroutunian V, Katsel P, Schmeidler J. Transcriptional vulnerability of brain regions in alzheimer's disease and dementia. Neurobiol Aging 2009, 30(4):561-573. 10.1016/j.neurobiolaging.2007.07.021, 2746014, 17845826.
12. Katsel P, Li C, Haroutunian V. Gene expression alterations in the sphingolipid metabolism pathways during progression of dementia and alzheimer's disease: A shift toward ceramide accumulation at the earliest recognizable stages of alzheimer's disease?. Neurochem Res 2007, 32(4-5):845-856.
13. Youn H, Jeoung M, Koo Y, Ji H, Markesbery WR, Ji I, Ji TH. Kalirin is under-expressed in alzheimer's disease hippocampus. J Alzheimers Dis 2007, 11(3):385-397.
14. Andrel JA, Keith SW, Leiby BE. Meta-analysis: A brief introduction. Clin Transl Sci 2009, 2(5):374-378. 10.1111/j.1752-8062.2009.00152.x, 20443922.
15. Campain A, Yang YH. Comparison study of microarray meta-analysis methods. BMC Bioinforma 2010, 11:408.
16. Murphy D. Gene expression studies using microarrays: Principles, problems, and prospects. Adv Physiol Educ 2002, 26(1-4):256-270.
17. Kong X, Mas V, Archer KJ. A non-parametric meta-analysis approach for combining independent microarray datasets: Application using two microarray datasets pertaining to chronic allograft nephropathy. BMC Genomics 2008, 9:98. 10.1186/1471-2164-9-98, 2276496, 18302764.
18. Braak H, Braak E. Neuropathological stageing of alzheimer-related changes. Acta Neuropathol 1991, 82(4):239-259. 10.1007/BF00308809, 1759558.
19. Irizarry RA, Warren D, Spencer F, Kim IF, Biswal S, Frank BC, Gabrielson E, Garcia JG, Geoghegan J, Germino G, Griffin C, Hilmer SC, Hoffman E, Jedlicka AE, Kawasaki E, Martinez-Murillo F, Morsberger L, Lee H, Petersen D, Quackenbush J, Scott A, Wilson M, Yang Y, Ye SQ, Yu W. Multiple-laboratory comparison of microarray platforms. Nat Methods 2005, 2(5):345-350. 10.1038/nmeth756, 15846361.
20. Cajigas IJ, Tushev G, Will TJ, Tom Dieck S, Fuerst N, Schuman EM. The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging. Neuron 2012, 74(3):453-466. 10.1016/j.neuron.2012.02.036, 3627340, 22578497.
21. De Franceschi L, Scardoni G, Tomelleri C, Danek A, Walker RH, Jung HH, Bader B, Mazzucco S, Dotti MT, Siciliano A, Pantaleo A, Laudanna C. Computational identification of phospho-tyrosine sub-networks related to acanthocyte generation in neuroacanthocytosis. PLoS One 2012, 7(2):e31015. 10.1371/journal.pone.0031015, 3280254, 22355334.
22. Barron AM, Pike CJ. Sex hormones, aging, and alzheimer's disease. Front Biosci (Elite Ed) 2012, 4:976-997.
23. Barbash S, Soreq H. Threshold-independent meta-analysis of alzheimer's disease transcriptomes shows progressive changes in hippocampal functions, epigenetics and microrna regulation. Curr Alzheimer Res 2012, 9(4):425-435. 10.2174/156720512800492512, 22191566.
24. Andersen K, Launer LJ, Dewey ME, Letenneur L, Ott A, Copeland JR, Dartigues JF, Kragh-Sorensen P, Baldereschi M, Brayne C, Lobo A, Martinez-Lage JM, Stijnen T, Hofman A. Gender differences in the incidence of ad and vascular dementia: The eurodem studies. Eurodem incidence research group. Neurology 1999, 53(9):1992-1997. 10.1212/WNL.53.9.1992, 10599770.
25. Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, D'Agostino RB, White LR. Prevalence of dementia and probable senile dementia of the alzheimer type in the framingham study. Neurology 1992, 42(1):115-119. 10.1212/WNL.42.1.115, 1734291.
26. Brayne C, Gill C, Huppert FA, Barkley C, Gehlhaar E, Girling DM, O'Connor DW, Paykel ES. Incidence of clinically diagnosed subtypes of dementia in an elderly population. Cambridge project for later life. Br J Psychiatry 1995, 167(2):255-262. 10.1192/bjp.167.2.255, 7582679.
27. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein e genotype and alzheimer disease. A meta-analysis. Apoe and alzheimer disease meta analysis consortium. JAMA 1997, 278(16):1349-1356. 10.1001/jama.1997.03550160069041, 9343467.
28. Fratiglioni L, Viitanen M, von Strauss E, Tontodonati V, Herlitz A, Winblad B. Very old women at highest risk of dementia and alzheimer's disease: Incidence data from the kungsholmen project, stockholm. Neurology 1997, 48(1):132-138. 10.1212/WNL.48.1.132, 9008508.
29. Hagnell O, Ojesjo L, Rorsman B. Incidence of dementia in the lundby study. Neuroepidemiology 1992, 11(Suppl 1):61-66.
30. Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: A quantitative integration of the literature. Acta Psychiatr Scand 1987, 76(5):465-479. 10.1111/j.1600-0447.1987.tb02906.x, 3324647.
31. Molsa PK, Marttila RJ, Rinne UK. Epidemiology of dementia in a finnish population. Acta Neurol Scand 1982, 65(6):541-552. 10.1111/j.1600-0404.1982.tb03109.x, 7113661.
32. Rocca WA, Amaducci LA, Schoenberg BS. Epidemiology of clinically diagnosed alzheimer's disease. Ann Neurol 1986, 19(5):415-424. 10.1002/ana.410190502, 3717905.
33. Ruitenberg A, Ott A, van Swieten JC, Hofman A, Breteler MM. Incidence of dementia: Does gender make a difference?. Neurobiol Aging 2001, 22(4):575-580. 10.1016/S0197-4580(01)00231-7, 11445258.
34. Callahan MJ, Lipinski WJ, Bian F, Durham RA, Pack A, Walker LC. Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice. Am J Pathol 2001, 158(3):1173-1177. 10.1016/S0002-9440(10)64064-3, 1850367, 11238065.
35. Hirata-Fukae C, Li HF, Hoe HS, Gray AJ, Minami SS, Hamada K, Niikura T, Hua F, Tsukagoshi-Nagai H, Horikoshi-Sakuraba Y, Mughal M, Rebeck GW, LaFerla FM, Mattson MP, Iwata N, Saido TC, Klein WL, Duff KE, Aisen PS, Matsuoka Y. Females exhibit more extensive amyloid, but not tau, pathology in an alzheimer transgenic model. Brain Res 2008, 1216:92-103.
36. Wang J, Tanila H, Puolivali J, Kadish I, van Groen T. Gender differences in the amount and deposition of amyloidbeta in appswe and ps1 double transgenic mice. Neurobiol Dis 2003, 14(3):318-327. 10.1016/j.nbd.2003.08.009, 14678749.
37. Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM. Estradiol modulates bcl-2 in cerebral ischemia: A potential role for estrogen receptors. J Neurosci 1999, 19(15):6385-6393.
38. Nilsen J, Diaz Brinton R. Mechanism of estrogen-mediated neuroprotection: Regulation of mitochondrial calcium and bcl-2 expression. Proc Natl Acad Sci USA 2003, 100(5):2842-2847. 10.1073/pnas.0438041100, 151428, 12604781.
39. Pike CJ. Estrogen modulates neuronal bcl-xl expression and beta-amyloid-induced apoptosis: Relevance to alzheimer's disease. J Neurochem 1999, 72(4):1552-1563.
40. Singer CA, Rogers KL, Dorsa DM. Modulation of bcl-2 expression: A potential component of estrogen protection in nt2 neurons. Neuroreport 1998, 9(11):2565-2568. 10.1097/00001756-199808030-00025, 9721933.
41. Stoltzner SE, Berchtold NC, Cotman CW, Pike CJ. Estrogen regulates bcl-x expression in rat hippocampus. Neuroreport 2001, 12(13):2797-2800. 10.1097/00001756-200109170-00009, 11588579.
42. Brinton RD, Chen S, Montoya M, Hsieh D, Minaya J. The estrogen replacement therapy of the women's health initiative promotes the cellular mechanisms of memory and neuronal survival in neurons vulnerable to alzheimer's disease. Maturitas 2000, 34(Suppl 2):S35-S52.
43. Nilsen J, Chen S, Brinton RD. Dual action of estrogen on glutamate-induced calcium signaling: Mechanisms requiring interaction between estrogen receptors and src/mitogen activated protein kinase pathway. Brain Res 2002, 930(1-2):216-234.
44. Regan RF, Guo Y. Estrogens attenuate neuronal injury due to hemoglobin, chemical hypoxia, and excitatory amino acids in murine cortical cultures. Brain Res 1997, 764(1-2):133-140.
45. Singer CA, Figueroa-Masot XA, Batchelor RH, Dorsa DM. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J Neurosci 1999, 19(7):2455-2463.
46. Singer CA, Rogers KL, Strickland TM, Dorsa DM. Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci Lett 1996, 212(1):13-16. 10.1016/0304-3940(96)12760-9, 8823751.
47. Singh M, Setalo G, Guan X, Warren M, Toran-Allerand CD. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: Convergence of estrogen and neurotrophin signaling pathways. J Neurosci 1999, 19(4):1179-1188.
48. Sastre M, Walter J, Gentleman SM. Interactions between app secretases and inflammatory mediators. J Neuroinflammation 2008, 5:25. 10.1186/1742-2094-5-25, 2442055, 18564425.
49. Vasto S, Candore G, Listi F, Balistreri CR, Colonna-Romano G, Malavolta M, Lio D, Nuzzo D, Mocchegiani E, Di Bona D, Caruso C. Inflammation, genes and zinc in alzheimer's disease. Brain Res Rev 2008, 58(1):96-105. 10.1016/j.brainresrev.2007.12.001, 18190968.
50. Behl C, Davis JB, Lesley R, Schubert D. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 1994, 77(6):817-827. 10.1016/0092-8674(94)90131-7, 8004671.
51. Mark RJ, Hensley K, Butterfield DA, Mattson MP. Amyloid beta-peptide impairs ion-motive atpase activities: Evidence for a role in loss of neuronal ca2+ homeostasis and cell death. J Neurosci 1995, 15(9):6239-6249.
52. Carlson MC, Zandi PP, Plassman BL, Tschanz JT, Welsh-Bohmer KA, Steffens DC, Bastian LA, Mehta KM, Breitner JC. Hormone replacement therapy and reduced cognitive decline in older women: The cache county study. Neurology 2001, 57(12):2210-2216. 10.1212/WNL.57.12.2210, 11756599.
53. Henderson VW, Paganini-Hill A, Emanuel CK, Dunn ME, Buckwalter JG. Estrogen replacement therapy in older women. Comparisons between alzheimer's disease cases and nondemented control subjects. Arch Neurol 1994, 51(9):896-900. 10.1001/archneur.1994.00540210068014, 8080389.
54. Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, Zonderman A, Bacal C, Lingle DD, Metter E. A prospective study of estrogen replacement therapy and the risk of developing alzheimer's disease: The baltimore longitudinal study of aging. Neurology 1997, 48(6):1517-1521. 10.1212/WNL.48.6.1517, 9191758.
55. Paganini-Hill A, Henderson VW. Estrogen deficiency and risk of alzheimer's disease in women. Am J Epidemiol 1994, 140(3):256-261.
56. Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of alzheimer disease. Arch Intern Med 1996, 156(19):2213-2217. 10.1001/archinte.1996.00440180075009, 8885820.
57. Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux R. Effect of oestrogen during menopause on risk and age at onset of alzheimer's disease. Lancet 1996, 348(9025):429-432. 10.1016/S0140-6736(96)03356-9, 8709781.
58. Waring SC, Rocca WA, Petersen RC, O'Brien PC, Tangalos EG, Kokmen E. Postmenopausal estrogen replacement therapy and risk of ad: A population-based study. Neurology 1999, 52(5):965-970. 10.1212/WNL.52.5.965, 10102413.
59. Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JC. Hormone replacement therapy and incidence of alzheimer disease in older women: The cache county study. JAMA 2002, 288(17):2123-2129. 10.1001/jama.288.17.2123, 12413371.
60. Hogervorst E, Boshuisen M, Riedel W, Willeken C, Jolles J. 1998 curt p. Richter award. The effect of hormone replacement therapy on cognitive function in elderly women. Psychoneuroendocrinology 1999, 24(1):43-68. 10.1016/S0306-4530(98)00043-2, 10098219.
61. LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: Systematic review and meta-analysis. JAMA 2001, 285(11):1489-1499. 10.1001/jama.285.11.1489, 11255426.
62. Ohkura T, Isse K, Akazawa K, Hamamoto M, Yaoi Y, Hagino N. Evaluation of estrogen treatment in female patients with dementia of the alzheimer type. Endocr J 1994, 41(4):361-371. 10.1507/endocrj.41.361, 8528351.
63. Sherwin BB. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology 1988, 13(4):345-357. 10.1016/0306-4530(88)90060-1, 3067252.
64. Almeida OP, Lautenschlager NT, Vasikaran S, Leedman P, Gelavis A, Flicker L. A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: Effect on mood, cognition and quality of life. Neurobiol Aging 2006, 27(1):141-149. 10.1016/j.neurobiolaging.2004.12.012, 16298249.
65. Barrett-Connor E, Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women. JAMA 1993, 269(20):2637-2641. 10.1001/jama.1993.03500200051032, 8487446.
66. Binder EF, Schechtman KB, Birge SJ, Williams DB, Kohrt WM. Effects of hormone replacement therapy on cognitive performance in elderly women. Maturitas 2001, 38(2):137-146. 10.1016/S0378-5122(00)00214-0, 11306202.
67. Brenner DE, Kukull WA, Stergachis A, van Belle G, Bowen JD, McCormick WC, Teri L, Larson EB. Postmenopausal estrogen replacement therapy and the risk of alzheimer's disease: A population-based case-control study. Am J Epidemiol 1994, 140(3):262-267.
68. Goebel JA, Birge SJ, Price SC, Hanson JM, Fishel DG. Estrogen replacement therapy and postural stability in the elderly. Am J Otol 1995, 16(4):470-474.
69. Henderson VW, Paganini-Hill A, Miller BL, Elble RJ, Reyes PF, Shoupe D, McCleary CA, Klein RA, Hake AM, Farlow MR. Estrogen for alzheimer's disease in women: Randomized, double-blind, placebo-controlled trial. Neurology 2000, 54(2):295-301. 10.1212/WNL.54.2.295, 10668686.
70. Polo-Kantola P, Portin R, Polo O, Helenius H, Irjala K, Erkkola R. The effect of short-term estrogen replacement therapy on cognition: A randomized, double-blind, cross-over trial in postmenopausal women. Obstet Gynecol 1998, 91(3):459-466. 10.1016/S0029-7844(97)00700-X, 9491878.
71. Wang PN, Liao SQ, Liu RS, Liu CY, Chao HT, Lu SR, Yu HY, Wang SJ, Liu HC. Effects of estrogen on cognition, mood, and cerebral blood flow in ad: A controlled study. Neurology 2000, 54(11):2061-2066. 10.1212/WNL.54.11.2061, 10851363.
72. Yaffe K, Krueger K, Sarkar S, Grady D, Barrett-Connor E, Cox DA, Nickelsen T. Cognitive function in postmenopausal women treated with raloxifene. N Eng J Med 2001, 344(16):1207-1213.
73. Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal LJ. Estrogen replacement therapy for treatment of mild to moderate alzheimer disease: A randomized controlled trial. Alzheimer's disease cooperative study. JAMA 2000, 283(8):1007-1015. 10.1001/jama.283.8.1007, 10697060.
74. Shao H, Breitner JC, Whitmer RA, Wang J, Hayden K, Wengreen H, Corcoran C, Tschanz J, Norton M, Munger R, Welsh-Bohmer K, Zandi PP. Hormone therapy and alzheimer disease dementia: New findings from the cache county study. Neurology 2012, 79(18):1846-1852. 10.1212/WNL.0b013e318271f823, 23100399.
75. Hestiantoro A, Swaab DF. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of alzheimer's disease neuropathology. J Clin Endocrinol Metab 2004, 89(4):1912-1925. 10.1210/jc.2003-030862, 15070964.
76. Kalesnykas G, Roschier U, Puolivali J, Wang J, Miettinen R. The effect of aging on the subcellular distribution of estrogen receptor-alpha in the cholinergic neurons of transgenic and wild-type mice. Eur J Neurosci 2005, 21(5):1437-1442. 10.1111/j.1460-9568.2005.03953.x, 15813954.
77. Lu YP, Zeng M, Swaab DF, Ravid R, Zhou JN. Colocalization and alteration of estrogen receptor-alpha and -beta in the hippocampus in alzheimer's disease. Hum Pathol 2004, 35(3):275-280. 10.1016/j.humpath.2003.11.004, 15017582.
78. Boulware MI, Mermelstein PG. The influence of estradiol on nervous system function. Drug News Perspect 2005, 18(10):631-637. 10.1358/dnp.2005.18.10.959577, 16491165.
79. Schupf N, Lee JH, Wei M, Pang D, Chace C, Cheng R, Zigman WB, Tycko B, Silverman W. Estrogen receptor-alpha variants increase risk of alzheimer's disease in women with down syndrome. Dement Geriatr Cogn Disord 2008, 25(5):476-482. 10.1159/000126495, 2430887, 18408366.
80. Kim H, Bang OY, Jung MW, Ha SD, Hong HS, Huh K, Kim SU, Mook-Jung I. Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells. Neurosci Lett 2001, 302(1):58-62. 10.1016/S0304-3940(01)01659-7, 11278111.
81. Cordey M, Pike CJ. Neuroprotective properties of selective estrogen receptor agonists in cultured neurons. Brain Res 2005, 1045(1-2):217-223.
82. Zhao L, Brinton RD. Estrogen receptor alpha and beta differentially regulate intracellular ca(2+) dynamics leading to erk phosphorylation and estrogen neuroprotection in hippocampal neurons. Brain Res 2007, 1172:48-59.
83. Zhao L, Wu TW, Brinton RD. Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased bcl-2 expression in primary hippocampal neurons. Brain Res 2004, 1010(1-2):22-34.
84. Atwood CS, Meethal SV, Liu T, Wilson AC, Gallego M, Smith MA, Bowen RL. Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence. J Neuropathol Exp Neurol 2005, 64(2):93-103.
85. Rosario ER, Pike CJ. Androgen regulation of beta-amyloid protein and the risk of alzheimer's disease. Brain Res Rev 2008, 57(2):444-453. 10.1016/j.brainresrev.2007.04.012, 2390933, 17658612.
86. Azcoitia I, Sierra A, Veiga S, Honda S, Harada N, Garcia-Segura LM. Brain aromatase is neuroprotective. J Neurobiol 2001, 47(4):318-329. 10.1002/neu.1038, 11351342.
87. Almeida OP, Flicker L. Testosterone and dementia: Too much ado about too little data. J Br Menopause Soc 2003, 9(3):107-110. 10.1258/136218003100322323, 14670195.
88. Gandy S, Almeida OP, Fonte J, Lim D, Waterrus A, Spry N, Flicker L, Martins RN. Chemical andropause and amyloid-beta peptide. JAMA 2001, 285(17):2195-2196. 10.1001/jama.285.17.2195, 11325319.
89. Gautier L, Moller M, Friis-Hansen L, Knudsen S. Alternative mapping of probes to genes for affymetrix chips. BMC Bioinforma 2004, 5:111.
90. Prieto C, Risueno A, Fontanillo C, De Las Rivas J. Human gene coexpression landscape: Confident network derived from tissue transcriptomic profiles. PLoS One 2008, 3(12):e3911. 10.1371/journal.pone.0003911, 2597745, 19081792.
91. Risueno A, Fontanillo C, Dinger ME, De Las Rivas J. Gatexplorer: Genomic and transcriptomic explorer; mapping expression probes to gene loci, transcripts, exons and ncrnas. BMC Bioinforma 2010, 11:221.
92. Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 2003, 19(2):185-193. 10.1093/bioinformatics/19.2.185, 12538238.
93. Hong F, Breitling R, McEntee CW, Wittner BS, Nemhauser JL, Chory J. Rankprod: A bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 2006, 22(22):2825-2827. 10.1093/bioinformatics/btl476, 16982708.
94. Berger SI, Posner JM, Ma'ayan A. Genes2networks: Connecting lists of gene symbols using mammalian protein interactions databases. BMC Bioinforma 2007, 8:372.
95. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: New features for data integration and network visualization. Bioinformatics 2011, 27(3):431-432. 10.1093/bioinformatics/btq675, 3031041, 21149340.
96. Scardoni G, Petterlini M, Laudanna C. Analyzing biological network parameters with centiscape. Bioinformatics 2009, 25(21):2857-2859. 10.1093/bioinformatics/btp517, 2781755, 19729372.
97. Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinforma 2003, 4:2.