Sex and gonadal hormones in mouse models of Alzheimer's disease: What is relevant to the human condition?

Biology of Sex Differences

Volumn 3, Issue 1, 2012, Pages

  Dubal, Dena B ^a   Broestl, Lauren ^a   Worden, Kurtresha ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

A ; Aging; Alzheimer's disease; Androgens; Andropause; Behavior; Brain; Cognition; Estrogen; Gender; Hormones; Human; Menopause; Mouse; Neurodegeneration; Pathology; Progesterone; Reproductive aging; Sex; Sex chromosomes; Tau; Testosterone; Transgenic

Indexed keywords

EID: 84892924069     PISSN: None     EISSN: 20426410     Source Type: Journal    
DOI: 10.1186/2042-6410-3-24     Document Type: Review

References (180)

1. Pankevich DE, Wizemann TM, Altevogt BM, Institute of Medicine (U.S.): Forum on Neuroscience and Nervous System Disorders. In Sex differences and implications for translational neuroscience research: workshop summary. Washington, D.C: National Academies Press; 2011.
2. Wimo A, Prince M: World Alzheimer Report 2010: the global economic impact of dementia. In Book World Alzheimer Report 2010: the global economic impact of dementia.: Alzheimer's Disease International (ADI); 2010:1-56.
3. Lindner MD, McArthur RA, Deadwyler SA, Hampson RE, Tariot PN: Chapter 4: Development, Optimization and Use of Preclinical Behavioral Models to Maximize the Productivity of Drug Discovery for Alzheimer's Disease. In Animal and Translational Models for CNS Drug Discovery. Volume 2: Neurological Disorders. Edited by McArthur R, Borsini F. San Diego: Academic Press; 2008:93-157.
4. Becker RE, Greig NH, Giacobini E: Why do so many drugs for Alzheimer's disease fail in development? Time for new methods and new practices? J Alzheimers Dis 2008, 15:303-325.
5. Huang Y, Mucke L: Alzheimer mechanisms and therapeutic strategies. Cell 2012, 148:1204-1222.
6. Palop JJ, Chin J, Mucke L: A network dysfunction perspective on neurodegenerative diseases. Nature 2006, 443:768-773. (Pubitemid 44622680)
7. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R: Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991, 30:572-580.
8. DeKosky ST, Scheff SW: Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 1990, 27:457-464. (Pubitemid 20149963)
9. Pievani M, de Haan W, Wu T, Seeley WW, Frisoni GB: Functional network disruption in the degenerative dementias. Lancet Neurol 2011, 10:829-843.
10. Palop JJ, Mucke L: Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat Neurosci 2010, 13:812-818.
11. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR: Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003, 60:1495-1500. (Pubitemid 36559525)
12. Villemagne VL, Ataka S, Mizuno T, Brooks WS, Wada Y, Kondo M, Jones G, Watanabe Y, Mulligan R, Nakagawa M, et al: High striatal amyloid betapeptide deposition across different autosomal Alzheimer disease mutation types. Arch Neurol 2009, 66:1537-1544.
13. Furst AJ, Rabinovici GD, Rostomian AH, Steed T, Alkalay A, Racine C, Miller BL, Jagust WJ: Cognition, glucose metabolism and amyloid burden in Alzheimer's disease. Neurobiol Aging 2012, 33:215-225.
14. Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A: Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 1988, 23:138-144. (Pubitemid 18081451)
15. Tomlinson BE, Blessed G, Roth M: Observations on the brains of non-demented old people. J Neurol Sci 1968, 7:331-356.
16. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR: Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 1999, 58:376-388. (Pubitemid 29187900)
17. Crystal HA, Dickson DW, Sliwinski MJ, Lipton RB, Grober E, Marks-Nelson H, Antis P: Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 1993, 34:566-573. (Pubitemid 23289408)
18. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman DM, Bacskai BJ, Hyman BT: Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 2008, 451:720-724. (Pubitemid 351220570)
19. Meyer-Luehmann M, Mielke M, Spires-Jones TL, Stoothoff W, Jones P, Bacskai BJ, Hyman BT: A reporter of local dendritic translocation shows plaque-related loss of neural system function in APP-transgenic mice. J Neurosci 2009, 29:12636-12640.
20. Spires-Jones TL, Kopeikina KJ, Koffie RM, de Calignon A, Hyman BT: Are tangles as toxic as they look? J Mol Neurosci 2011, 45:438-444.
21. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L: High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 2000, 20:4050-4058. (Pubitemid 30365675)
22. Klein WL, Krafft GA, Finch CE: Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum? Trends Neurosci 2001, 24:219-224. (Pubitemid 32204378)
23. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM: Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003, 39:409-421. (Pubitemid 36937044)
24. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, et al: Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005, 309:476-481. (Pubitemid 40994688)
25. Haroutunian V, Purohit DP, Perl DP, Marin D, Khan K, Lantz M, Davis KL, Mohs RC: Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch Neurol 1999, 56:713-718. (Pubitemid 29266472)
26. O'Leary JC 3rd, Li Q, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J 3rd, Jones JR, Kraft C, et al: Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener 2010, 5:45.
27. Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G, Mandelkow E, et al: Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 2011, 31:2511-2525.
28. Morris M, Maeda S, Vossel K, Mucke L: The many faces of tau. Neuron 2011, 70:410-426.
29. Yaffe K, Barnes E: Chapter 9: Epidemiology and risk factors. In The Behavioral Neurology of Dementia. Edited by Miller BL, Boeve BF. New York: Cambridge University Press; 2009.
30. Bertram L, Lill CM, Tanzi RE: The genetics of Alzheimer disease: back to the future. Neuron 2010, 68:270-281.
31. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993, 261:921-923. (Pubitemid 23275809)
32. 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, 278:1349-1356. (Pubitemid 27449696)
33. Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, Bullido MJ, Engelborghs S, De Deyn P, Berr C, et al: APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry 2011, 16:903-907.
34. Logue MW, Schu M, Vardarajan BN, Buros J, Green RC, Go RC, Griffith P, Obisesan TO, Shatz R, Borenstein A, et al: A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 2011, 68:1569-1579.
35. Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, et al: A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 2012.
36. Tanzi RE, Bertram L: Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 2005, 120:545-555. (Pubitemid 40269768)
37. Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ: Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci 2011, 31:6627-6638.
38. Yu W, Lu B: Synapses and dendritic spines as pathogenic targets in Alzheimer's disease. Neural Plast 2012, 2012:247150.
39. Zempel H, Thies E, Mandelkow E, Mandelkow EM: Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci 2010, 30:11938-11950.
40. Palop JJ, Mucke L: Synaptic depression and aberrant excitatory network activity in Alzheimer's disease: two faces of the same coin? Neuromolecular Med 2010, 12:48-55.
41. Claus JJ, van Gool WA, Teunisse S, Walstra GJ, Kwa VI, Hijdra A, Verbeeten B Jr, Koelman JH, Bour LJ, Ongerboer De Visser BW: Predicting survival in patients with early Alzheimer's disease. Dement Geriatr Cogn Disord 1998, 9:284-293. (Pubitemid 28377229)
42. Ueki A, Shinjo H, Shimode H, Nakajima T, Morita Y: Factors associated with mortality in patients with early-onset Alzheimer's disease: a five-year longitudinal study. Int J Geriatr Psychiatry 2001, 16:810-815. (Pubitemid 32834119)
43. Heyman A, Wilkinson WE, Hurwitz BJ, Helms MJ, Haynes CS, Utley CM, Gwyther LP: Early-onset Alzheimer's disease: clinical predictors of institutionalization and death. Neurology 1987, 37:980-984. (Pubitemid 17081072)
44. Stern Y, Tang MX, Albert MS, Brandt J, Jacobs DM, Bell K, Marder K, Sano M, Devanand D, Albert SM, et al: Predicting time to nursing home care and death in individuals with Alzheimer disease. JAMA 1997, 277:806-812. (Pubitemid 27111316)
45. Lapane KL, Gambassi G, Landi F, Sgadari A, Mor V, Bernabei R: Gender differences in predictors of mortality in nursing home residents with AD. Neurology 2001, 56:650-654. (Pubitemid 32210000)
46. Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA: Is the risk of developing Alzheimer's disease greater for women than for men? Am J Epidemiol 2001, 153:132-136. (Pubitemid 32060603)
47. Petersen RC, Roberts RO, Knopman DS, Geda YE, Cha RH, Pankratz VS, Boeve BF, Tangalos EG, Ivnik RJ, Rocca WA: Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study of Aging. Neurology 2010, 75:889-897.
48. Ganguli M, Dodge HH, Shen C, DeKosky ST: Mild cognitive impairment, amnestic type: an epidemiologic study. Neurology 2004, 63:115-121. (Pubitemid 38943788)
49. Koivisto K, Reinikainen KJ, Hanninen T, Vanhanen M, Helkala EL, Mykkanen L, Laakso M, Pyorala K, Riekkinen PJ Sr: Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland. Neurology 1995, 45:741-747.
50. Luck T, Luppa M, Briel S, Matschinger H, Konig HH, Bleich S, Villringer A, Angermeyer MC, Riedel-Heller SG: Mild cognitive impairment: incidence and risk factors: results of the leipzig longitudinal study of the aged. J Am Geriatr Soc 2010, 58:1903-1910.
51. Kivipelto M, Helkala EL, Hanninen T, Laakso MP, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A: Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study. Neurology 2001, 56:1683-1689. (Pubitemid 32574567)
52. Jorm AF, Jolley D: The incidence of dementia: a meta-analysis. Neurology 1998, 51:728-733. (Pubitemid 28449250)
53. Roberts RO, Geda YE, Knopman DS, Cha RH, Pankratz VS, Boeve BF, Tangalos EG, Ivnik RJ, Rocca WA, Petersen RC: The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging. Neurology 2012, 78:342-351.
54. Hui JS, Wilson RS, Bennett DA, Bienias JL, Gilley DW, Evans DA: Rate of cognitive decline and mortality in Alzheimer's disease. Neurology 2003, 61:1356-1361. (Pubitemid 37463370)
55. Caracciolo B, Palmer K, Monastero R, Winblad B, Backman L, Fratiglioni L: Occurrence of cognitive impairment and dementia in the community: a 9-year-long prospective study. Neurology 2008, 70:1778-1785. (Pubitemid 351653963)
56. Chakravarti S, Collins WP, Forecast JD, Newton JR, Oram DH, Studd JW: Hormonal profiles after the menopause. Br Med J 1976, 2:784-787.
57. Veldhuis JD: Aging and hormones of the hypothalamo-pituitary axis: gonadotropic axis in men and somatotropic axes in men and women. Ageing Res Rev 2008, 7:189-208.
58. Ferrini RL, Barrett-Connor E: Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 1998, 147:750-754. (Pubitemid 28183274)
59. Merry BJ, Holehan AM: Aging of the Female Reproductive System: The Menopause. In Physiological Basis of Aging and Geriatrics. 2nd edition. Edited by Timiras PS. Boca Raton: CRC Press, Inc; 1994:147-170.
60. Morley JE, Kaiser F, Raum WJ, Perry HM 3rd, Flood JF, Jensen J, Silver AJ, Roberts E: Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci U S A 1997, 94:7537-7542.
61. Nelson JF, Latham KR, Finch CE: Plasma testosterone levels in C57BL/6J male mice: effects of age and disease. Acta Endocrinol (Copenh) 1975, 80:744-752.
62. Nelson JF, Felicio LS, Osterburg HH, Finch CE: Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice. Endocrinology 1992, 130:805-810.
63. Finch CE, Jonec V, Wisner JR Jr, Sinha YN, de Vellis JS, Swerdloff RS: Hormone production by the pituitary and testes of male C57BL/6J mice during aging. Endocrinology 1977, 101:1310-1317. (Pubitemid 8187579)
64. Eleftheriou BE, Lucas LA: Age-related changes in testes, seminal vesicles and plasma testosterone levels in male mice. Gerontologia 1974, 20:231-238.
65. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, et al: Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003, 289:2651-2662. (Pubitemid 37430136)
66. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, et al: Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004, 291:2947-2958. (Pubitemid 38802684)
67. Grady D, Yaffe K, Kristof M, Lin F, Richards C, Barrett-Connor E: Effect of postmenopausal hormone therapy on cognitive function: the heart and estrogen/progestin replacement study. Am J Med 2002, 113:543-548. (Pubitemid 35379908)
68. Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, et al: Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study. JAMA 2000, 283:1007-1015. (Pubitemid 30112214)
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, 54:295-301. (Pubitemid 30078056)
70. 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, 54:2061-2066. (Pubitemid 30397202)
71. Wise PM, Suzuki S, Brown CM: Estradiol: a hormone with diverse and contradictory neuroprotective actions. Dialogues Clin Neurosci 2009, 11:297-303.
72. Turgeon JL, McDonnell DP, Martin KA, Wise PM: Hormone therapy: physiological complexity belies therapeutic simplicity. Science 2004, 304:1269-1273. (Pubitemid 38697412)
73. Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N: KEEPS: the Kronos Early Estrogen Prevention Study. Climacteric 2005, 8:3-12. (Pubitemid 40675116)
74. Golde TE, Schneider LS, Koo EH: Anti-abeta therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron 2011, 69:203-213.
75. Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ: Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010, 9:119-128.
76. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB: Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metabol 2002, 87:589-598. (Pubitemid 34158223)
77. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR: Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metabol 2001, 86:724-731. (Pubitemid 32207487)
78. Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN, Garry PJ: Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism: clinical and experimental 1997, 46:410-413. (Pubitemid 27172090)
79. Liu PY, Beilin J, Meier C, Nguyen TV, Center JR, Leedman PJ, Seibel MJ, Eisman JA, Handelsman DJ: Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metabol 2007, 92:3599-3603. (Pubitemid 47435341)
80. Hammond GL: Access of reproductive steroids to target tissues. Obstet Gynecol Clin North Am 2002, 29:411-423.
81. Hammond GL: Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod 2011, 85:431-441.
82. Muller M, Schupf N, Manly JJ, Mayeux R, Luchsinger JA: Sex hormone binding globulin and incident Alzheimer's disease in elderly men and women. Neurobiol Aging 2010, 31:1758-1765.
83. Hoskin EK, Tang MX, Manly JJ, Mayeux R: Elevated sex-hormone binding globulin in elderly women with Alzheimer's disease. Neurobiol Aging 2004, 25:141-147. (Pubitemid 38121687)
84. Paoletti AM, Congia S, Lello S, Tedde D, Orru M, Pistis M, Pilloni M, Zedda P, Loddo A, Melis GB: Low androgenization index in elderly women and elderly men with Alzheimer's disease. Neurology 2004, 62:301-303. (Pubitemid 38167146)
85. Rosario ER, Pike CJ: Androgen regulation of beta-amyloid protein and the risk of Alzheimer's disease. Brain Res Rev 2008, 57:444-453. (Pubitemid 351384807)
86. Fitzgerald C, Zimon AE, Jones EE: Aging and reproductive potential in women. Yale J Biol Med 1998, 71:367-381.
87. Downs JL, Wise PM: The role of the brain in female reproductive aging. Mol Cell Endocrinol 2009, 299:32-38.
88. Kermath BA, Gore AC: Neuroendocrine control of the transition to reproductive senescence: lessons learned from the female rodent model. Neuroendocrinology 2012, 96:1-12.
89. Mobbs CV, Gee DM, Finch CE: Reproductive senescence in female C57BL/6J mice: ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy. Endocrinology 1984, 115:1653-1662. (Pubitemid 15206576)
90. Mayer LP, Devine PJ, Dyer CA, Hoyer PB: The follicle-deplete mouse ovary produces androgen. Biol Reprod 2004, 71:130-138. (Pubitemid 38915317)
91. Arnold AP, Chen X: What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues? Front Neuroendocrinol 2009, 30:1-9.
92. McCarthy MM, Arnold AP, Ball GF, Blaustein JD, De Vries GJ: Sex differences in the brain: the not so inconvenient truth. J Neurosci 2012, 32:2241-2247.
93. Baker HW, Burger HG, de Kretser DM, Hudson B, O'Connor S, Wang C, Mirovics A, Court J, Dunlop M, Rennie GC: Changes in the pituitarytesticular system with age. Clin Endocrinol (Oxf) 1976, 5:349-372.
94. Hale GE, Burger HG: Hormonal changes and biomarkers in late reproductive age, menopausal transition and menopause. Best Pract Res Clin Obstet Gynaecol 2009, 23:7-23.
95. Ostergard DR, Parlow AF, Townsend DE: Acute effect of castration on serum FSH and LH in the adult woman. J Clin Endocrinol Metabol 1970, 31:43-47.
96. Monroe SE, Jaffee RB, Midgley AJ: Regulation of human gonadotropins: 13. Changes in serum gonadotropins in menstruating women in response to oophorectomy. J Clin Endocrinol 1972, 34:420-422.
97. Naik SI, Young LS, Charlton HM, Clayton RN: Pituitary gonadotropin releasing hormone receptor regulation in mice. II: Females. Endocrinology 1984, 115:114-120. (Pubitemid 14086799)
98. Naik SI, Young LS, Charlton HM, Clayton RN: Pituitary gonadotropin releasing hormone receptor regulation in mice. I: Males. Endocrinology 1984, 115:106-113. (Pubitemid 14086798)
99. Danilovich N, Babu PS, Xing W, Gerdes M, Krishnamurthy H, Sairam MR: Estrogen deficiency, obesity, and skeletal abnormalities in follicle-stimulating hormone receptor knockout (FORKO) female mice. Endocrinology 2000, 141:4295-4308.
100. Danilovich N, Maysinger D, Sairam MR: Perspectives on reproductive senescence and biological aging: studies in genetically altered follitropin receptor knockout [FORKO] mice. Exp Gerontol 2004, 39:1669-1678. (Pubitemid 39576138)
101. Jucker M: The benefits and limitations of animal models for translational research in neurodegenerative diseases. Nat Med 2010, 16:1210-1214.
102. Ashe KH, Zahs KR: Probing the biology of Alzheimer's disease in mice. Neuron 2010, 66:631-645.
103. Roberson ED: Contemporary approaches to Alzheimer's disease and frontotemporal dementia. Methods Mol Biol 2011, 670:1-9.
104. Hoe HS, Lee HK, Pak DT: The upside of APP at synapses. CNS Neurosci Ther 2012, 18:47-56.
105. Lazarov O, Demars MP: All in the Family: how the APPs Regulate Neurogenesis. Front Neurosci 2012, 6:81.
106. Reaume AG, Howland DS, Trusko SP, Savage MJ, Lang DM, Greenberg BD, Siman R, Scott RW: Enhanced amyloidogenic processing of the beta-amyloid precursor protein in gene-targeted mice bearing the Swedish familial Alzheimer's disease mutations and a "humanized" Abeta sequence. J Biol Chem 1996, 271:23380-23388. (Pubitemid 26314785)
107. Flood DG, Reaume AG, Dorfman KS, Lin YG, Lang DM, Trusko SP, Savage MJ, Annaert WG, De Strooper B, Siman R, Scott RW: FAD mutant PS-1 genetargeted mice: increased A beta 42 and A beta deposition without APP overproduction. Neurobiol Aging 2002, 23:335-348. (Pubitemid 34312016)
108. Malthankar-Phatak GH, Lin YG, Giovannone N, Siman R: Amyloid deposition and advanced age fails to induce Alzheimer's type progression in a double knock-in mouse model. Aging dis 2012, 3:141-155.
109. Morris RG: Episodic-like memory in animals: psychological criteria, neural mechanisms and the value of episodic-like tasks to investigate animal models of neurodegenerative disease. Philos Trans R Soc Lond B Biol Sci 2001, 356:1453-1465. (Pubitemid 32948870)
110. Maguire JL, Stell BM, Rafizadeh M, Mody I: Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat Neurosci 2005, 8:797-804. (Pubitemid 43085847)
111. Fata JE, Chaudhary V, Khokha R: Cellular turnover in the mammary gland is correlated with systemic levels of progesterone and not 17beta-estradiol during the estrous cycle. Biol Reprod 2001, 65:680-688. (Pubitemid 32777350)
112. Walmer DK, Wrona MA, Hughes CL, Nelson KG: Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone. Endocrinology 1992, 131:1458-1466.
113. Wood GA, Fata JE, Watson KL, Khokha R: Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus. Reproduction 2007, 133:1035-1044. (Pubitemid 47162593)
114. Melnikova T, Savonenko A, Wang Q, Liang X, Hand T, Wu L, Kaufmann WE, Vehmas A, Andreasson KI: Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern. Neuroscience 2006, 141:1149-1162. (Pubitemid 44128685)
115. Clinton LK, Billings LM, Green KN, Caccamo A, Ngo J, Oddo S, McGaugh JL, LaFerla FM: Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 2007, 28:76-82. (Pubitemid 47429975)
116. Carroll JC, Rosario ER, Kreimer S, Villamagna A, Gentzschein E, Stanczyk FZ, Pike CJ: Sex differences in beta-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure. Brain Res 2010, 1366:233-245.
117. Pietropaolo S, Sun Y, Li R, Brana C, Feldon J, Yee BK: The impact of voluntary exercise on mental health in rodents: a neuroplasticity perspective. Behav Brain Res 2008, 192:42-60.
118. Gimenez-Llort L, Garcia Y, Buccieri K, Revilla S, Sunol C, Cristofol R, Sanfeliu C: Gender-specific neuroimmunoendocrine response to treadmill exercise in 3xTg-AD Mice. Int J Alzheimers Dis 2010, 2010:128354.
119. King DL, Arendash GW, Crawford F, Sterk T, Menendez J, Mullan MJ: Progressive and gender-dependent cognitive impairment in the APP (SW) transgenic mouse model for Alzheimer's disease. Behav Brain Res 1999, 103:145-162. (Pubitemid 29417998)
120. Gimenez-Llort L, Arranz L, Mate I, De la Fuente M: Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer's disease and its relation with longevity. Neuroimmunomodulation 2008, 15:331-343.
121. Howlett DR, Richardson JC, Austin A, Parsons AA, Bate ST, Davies DC, Gonzalez MI: Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Res 2004, 1017:130-136. (Pubitemid 38917152)
122. O'Leary TP, Brown RE: Visuo-spatial learning and memory deficits on the Barnes maze in the 16-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease. Behav Brain Res 2009, 201:120-127.
123. Hirata-Fukae C, Li HF, Hoe HS, Gray AJ, Minami SS, Hamada K, Niikura T, Hua F, Tsukagoshi-Nagai H, Horikoshi-Sakuraba Y, et al: Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res 2008, 1216:92-103.
124. Callahan MJ, Lipinski WJ, Bian F, Durham RA, Pack A, Walker LC: Augmented senile plaque load in aged female beta-amyloid precursor proteintransgenic mice. Am J Pathol 2001, 158:1173-1177. (Pubitemid 32221809)
125. Schafer S, Wirths O, Multhaup G, Bayer TA: Gender dependent APP processing in a transgenic mouse model of Alzheimer's disease. J Neural Transm 2007, 114:387-394. (Pubitemid 46328658)
126. 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, 14:318-327. (Pubitemid 37543511)
127. Pistell PJ, Zhu M, Ingram DK: Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease. Neuroscience 2008, 152:594-600.
128. Perez SE, Berg BM, Moore KA, He B, Counts SE, Fritz JJ, Hu YS, Lazarov O, Lah JJ, Mufson EJ: DHA diet reduces AD pathology in young APPswe/PS1 Delta E9 transgenic mice: possible gender effects. J Neurosci Res 2010, 88:1026-1040.
129. Lin J, Li X, Yuan F, Lin L, Cook CL, Rao CV, Lei Z: Genetic ablation of luteinizing hormone receptor improves the amyloid pathology in a mouse model of Alzheimer disease. J Neuropathol Exp Neurol 2010, 69:253-261.
130. Schuessel K, Schafer S, Bayer TA, Czech C, Pradier L, Muller-Spahn F, Muller WE, Eckert A: Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol Dis 2005, 18:89-99. (Pubitemid 40092899)
131. Minami SS, Sidahmed E, Aid S, Shimoji M, Niikura T, Mocchetti I, Rebeck GW, Prendergast JS, Dealwis C, Wetzel R, et al: Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Abeta/amyloid burden in a transgenic mouse model of Alzheimer's disease. J Neuroinflammation 2010, 7:57.
132. Oliveira SM, Ribeiro CA, Cardoso I, Saraiva MJ: Gender-dependent transthyretin modulation of brain amyloid-beta levels: evidence from a mouse model of Alzheimer's disease. J Alzheimers Dis 2011, 27:429-439.
133. Pacheco-Quinto J, de Turco EB R, DeRosa S, Howard A, Cruz-Sanchez F, Sambamurti K, Refolo L, Petanceska S, Pappolla MA: Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid beta peptide levels. Neurobiol Dis 2006, 22:651-656. (Pubitemid 43832135)
134. Park IH, Hwang EM, Hong HS, Boo JH, Oh SS, Lee J, Jung MW, Bang OY, Kim SU, Mook-Jung I: Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Neurobiol Aging 2003, 24:637-643. (Pubitemid 37288863)
135. Touma C, Ambree O, Gortz N, Keyvani K, Lewejohann L, Palme R, Paulus W, Schwarze-Eicker K, Sachser N: Age-and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer's disease. Neurobiol Aging 2004, 25:893-904. (Pubitemid 38813169)
136. Overk CR, Lu PY, Wang YT, Choi J, Shaw JW, Thatcher GR, Mufson EJ: Effects of aromatase inhibition versus gonadectomy on hippocampal complex amyloid pathology in triple transgenic mice. Neurobiol Dis 2012, 45:479-487.
137. Devi L, Alldred MJ, Ginsberg SD, Ohno M: Sex-and brain region-specific acceleration of beta-amyloidogenesis following behavioral stress in a mouse model of Alzheimer's disease. Mol Brain 2010, 3:34.
138. Lee JY, Cole TB, Palmiter RD, Suh SW, Koh JY: Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci U S A 2002, 99:7705-7710. (Pubitemid 34568755)
139. Oikawa N, Ogino K, Masumoto T, Yamaguchi H, Yanagisawa K: Gender effect on the accumulation of hyperphosphorylated tau in the brain of locusceruleus-injured APP-transgenic mouse. Neurosci Lett 2010, 468:243-247.
140. Maynard CJ, Cappai R, Volitakis I, Cherny RA, Masters CL, Li QX, Bush AI: Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology. J Inorg Biochem 2006, 100:952-962.
141. Nakashima AS, Oddo S, Laferla FM, Dyck RH: Experience-dependent regulation of vesicular zinc in male and female 3xTg-AD mice. Neurobiol Aging 2010, 31:605-613.
142. Barrier L, Ingrand S, Fauconneau B, Page G: Gender-dependent accumulation of ceramides in the cerebral cortex of the APP(SL)/PS1Ki mouse model of Alzheimer's disease. Neurobiol Aging 2010, 31:1843-1853.
143. Ash ES, Alavijeh MS, Palmer AM, Mitchelmore C, Howlett DR, Francis PT, Broadstock M, Richardson JC: Neurochemical changes in a double transgenic mouse model of Alzheimer's disease fed a pro-oxidant diet. Neurochem Int 2010, 57:504-511.
144. Hsiao KK, Borchelt DR, Olson K, Johannsdottir R, Kitt C, Yunis W, Xu S, Eckman C, Younkin S, Price D, et al: Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 1995, 15:1203-1218.
145. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, et al: Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 2007, 55:697-711. (Pubitemid 47321079)
146. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L: Reducing endogenous tau ameliorates amyloid betainduced deficits in an Alzheimer's disease mouse model. Science 2007, 316:750-754. (Pubitemid 46717684)
147. Roberson ED, Halabisky B, Yoo JW, Yao J, Chin J, Yan F, Wu T, Hamto P, Devidze N, Yu GQ, et al: Amyloid-beta/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J Neurosci 2011, 31:700-711.
148. Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fulop L, Penke B, Zilberter Y, Harkany T, Pitkanen A, Tanila H: Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 2009, 29:3453-3462.
149. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wolfing H, Chieng BC, Christie MJ, Napier IA, et al: Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 2010, 142:387-397.
150. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, et al: Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 2012, 149:708-721.
151. Woolley CS: Acute effects of estrogen on neuronal physiology. Annu Rev Pharmacol Toxicol 2007, 47:657-680.
152. Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS: Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol 2008, 29:219-237.
153. Foy MR, Baudry M, Diaz Brinton R, Thompson RF: Estrogen and hippocampal plasticity in rodent models. J Alzheimers Dis 2008, 15:589-603.
154. Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J: Progesterone receptors: form and function in brain. Front Neuroendocrinol 2008, 29:313-339.
155. Holland J, Bandelow S, Hogervorst E: Testosterone levels and cognition in elderly men: a review. Maturitas 2011, 69:322-337.
156. Pike CJ, Nguyen TV, Ramsden M, Yao M, Murphy MP, Rosario ER: Androgen cell signaling pathways involved in neuroprotective actions. Horm Behav 2008, 53:693-705.
157. Frye CA: Neurosteroids' effects and mechanisms for social, cognitive, emotional, and physical functions. Psychoneuroendocrinology 2009, 34(Suppl 1):S143-161.
158. Wang JM, Liu L, Irwin RW, Chen S, Brinton RD: Regenerative potential of allopregnanolone. Brain Res Rev 2008, 57:398-409. (Pubitemid 351381778)
159. Heikkinen T, Kalesnykas G, Rissanen A, Tapiola T, Iivonen S, Wang J, Chaudhuri J, Tanila H, Miettinen R, Puolivali J: Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation. Exp Neurol 2004, 187:105-117. (Pubitemid 38470017)
160. Golub MS, Germann SL, Mercer M, Gordon MN, Morgan DG, Mayer LP, Hoyer PB: Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse. Neurobiol Aging 2008, 29:1512-1523.
161. Levin-Allerhand JA, Lominska CE, Wang J, Smith JD: 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in A beta PPSWE transgenic mice. J Alzheimers Dis 2002, 4:449-457. (Pubitemid 36142834)
162. Carroll JC, Pike CJ: Selective estrogen receptor modulators differentially regulate Alzheimer-like changes in female 3xTg-AD mice. Endocrinology 2008, 149:2607-2611. (Pubitemid 351574524)
163. Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ: Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci 2007, 27:13357-13365. (Pubitemid 350220504)
164. Carroll JC, Rosario ER, Villamagna A, Pike CJ: Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTransgenic-Alzheimer's disease mice. Endocrinology 2010, 151:2713-2722.
165. Zhao L, Yao J, Mao Z, Chen S, Wang Y, Brinton RD: 17beta-Estradiol regulates insulin-degrading enzyme expression via an ERbeta/PI3-K pathway in hippocampus: relevance to Alzheimer's prevention. Neurobiol Aging 2011, 32:1949-1963.
166. Xu H, Wang R, Zhang YW, Zhang X: Estrogen, beta-amyloid metabolism/trafficking, and Alzheimer's disease. Ann N Y Acad Sci 2006, 1089:324-342. (Pubitemid 47092091)
167. Zheng H, Xu H, Uljon SN, Gross R, Hardy K, Gaynor J, Lafrancois J, Simpkins J, Refolo LM, Petanceska S, et al: Modulation of A(beta) peptides by estrogen in mouse models. J Neurochem 2002, 80:191-196. (Pubitemid 34614591)
168. Amtul Z, Wang L, Westaway D, Rozmahel RF: Neuroprotective mechanism conferred by 17beta-estradiol on the biochemical basis of Alzheimer's disease. Neuroscience 2010, 169:781-786.
169. Frye CA, Walf AA: Effects of progesterone administration and APPswe +PSEN1Deltae9 mutation for cognitive performance of mid-aged mice. Neurobiol Learn Mem 2008, 89:17-26. (Pubitemid 350102253)
170. Green PS, Bales K, Paul S, Bu G: Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease. Endocrinology 2005, 146:2774-2781. (Pubitemid 40695582)
171. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, Harada N, Zhong Z, Shen Y, Li R: Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer's disease animal model. Proc Natl Acad Sci U S A 2005, 102:19198-19203. (Pubitemid 43049589)
172. Levin-Allerhand JA, Smith JD: Ovariectomy of young mutant amyloid precursor protein transgenic mice leads to increased mortality. J Mol Neurosci 2002, 19:163-166. (Pubitemid 35013350)
173. Hogervorst E, Williams J, Budge M, Barnetson L, Combrinck M, Smith AD: Serum total testosterone is lower in men with Alzheimer's disease. Neuro Endocrinol Lett 2001, 22:163-168. (Pubitemid 32677235)
174. Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM: Free testosterone and risk for Alzheimer disease in older men. Neurology 2004, 62:188-193. (Pubitemid 38167123)
175. Rosario ER, Chang L, Stanczyk FZ, Pike CJ: Age-related testosterone depletion and the development of Alzheimer disease. JAMA 2004, 292:1431-1432. (Pubitemid 39258334)
176. Moffat SD: Does testosterone mediate cognitive decline in elderly men? J Gerontol A Biol Sci Med Sci 2006, 61:521. (Pubitemid 43794714)
177. Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ: Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J Neurosci 2006, 26:13384-13389. (Pubitemid 46011649)
178. McAllister C, Long J, Bowers A, Walker A, Cao P, Honda S, Harada N, Staufenbiel M, Shen Y, Li R: Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment. J Neurosci 2010, 30:7326-7334.
179. Rosario ER, Carroll J, Pike CJ: Testosterone regulation of Alzheimer-like neuropathology in male 3xTg-AD mice involves both estrogen and androgen pathways. Brain Res 2010, 1359:281-290.
180. Casadesus G, Webber KM, Atwood CS, Pappolla MA, Perry G, Bowen RL, Smith MA: Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice. Biochim Biophys Acta 2006, 1762:447-452. (Pubitemid 43344306)