Androgens and Alzheimer's disease

Current Opinion in Endocrinology, Diabetes and Obesity

Volumn 16, Issue 3, 2009, Pages 254-259

  Drummond, Eleanor S ^a   Harvey, Alan R ^a   Martins, Ralph N ^a,b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b EDITH COWAN UNIVERSITY   (Australia)

Author keywords

Alzheimer's disease; Androgen; Beta amyloid; Luteinizing hormone; Phosphorylated tau; Testosterone

Indexed keywords

AMYLOID BETA PROTEIN; ANDROGEN; GONADOTROPIN; TAU PROTEIN;

ALZHEIMER DISEASE; CELL DEATH; COGNITION; DEATH; DISEASE ASSOCIATION; HORMONE BLOOD LEVEL; HUMAN; MEMORY; MOLECULAR MECHANICS; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN PHOSPHORYLATION; REVIEW; RISK FACTOR; SUPPLEMENTATION; TASK PERFORMANCE; AGING; ANIMAL; DOWN REGULATION; DRUG EFFECT; FEMALE; HORMONE SUBSTITUTION; MALE; METABOLISM; NERVE CELL; PATHOLOGY; PHOSPHORYLATION; PSYCHOLOGICAL ASPECT; TREATMENT OUTCOME;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANDROGENS; ANIMALS; CELL DEATH; COGNITION; DOWN-REGULATION; FEMALE; GONADOTROPINS; HORMONE REPLACEMENT THERAPY; HUMANS; MALE; MEMORY; NEURONS; PHOSPHORYLATION; RISK FACTORS; TAU PROTEINS; TREATMENT OUTCOME;

EID: 66349083606     PISSN: 1752296X     EISSN: None     Source Type: Journal    
DOI: 10.1097/MED.0b013e32832b101f     Document Type: Review

References (66)

1. Tohgi H, Utsugisawa K, Yamagata M, Yoshimura M. Effects of age on messenger RNA expression of glucocorticoid, thyroid hormone, androgen and estrogen receptors in postmortem human hippocampus. Brain Res 1995; 700:245-253.
2. Puy L, MacLusky NJ, Becker L, et al. Immunocytochemical detection of androgen receptor in human temporal cortex characterization and application of polyclonal androgen receptor antibodies in frozen and paraffin-embedded tissues. J Steroid Biochem Mol Biol 1995; 55:197-209.
3. Fernandez-Guasti A, Kruijver FP, Fodor M, Swaab DF. Sex differences in the distribution of androgen receptors in the human hypothalamus. J Comp Neurol 2000; 425:422-435. (Pubitemid 30659207)
4. Beyenburg S, Watzka M, Clusmann H, et al. Androgen receptor mRNA expression in the human hippocampus. Neurosci Lett 2000; 294:25-28. (Pubitemid 30758994)
5. Pak TR, Chung WC, Lund TD, et al. The androgen metabolite, 5alphaandrostane-3beta, 17beta-diol, is a potent modulator of estrogen receptorbeta1-mediated gene transcription in neuronal cells. Endocrinology 2005; 146:147-155.
6. Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male ageing study. J Clin Endocrinol Metab 2002; 87:589-598. (Pubitemid 34158223)
7. Liu PY, Beilin J, Meier C, et al. 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 Metab 2007; 92:3599-3603. (Pubitemid 47435341)
8. Gapstur SM, Gann PH, Kopp P, et al. Serum androgen concentrations in young men: a longitudinal analysis of associations with age, obesity, and race. The CARDIA male hormone study. Cancer Epidemiol Biomarkers Prev 2002; 11:1041-1047.
9. Travison TG, Araujo A, O'Donnell AB, et al. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab 2007; 92:196-202. (Pubitemid 46075010)
10. Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001; 86:724-731.
11. T'Sjoen GG, De Vos S, Goemaere S, et al. Sex steroid level, androgen receptor polymorphism, and depressive symptoms in healthy elderly men. J Am Geriatr Soc 2005; 53:636-642. (Pubitemid 41623486)
12. Bo M, Massaia M, Zannella P, et al. Dehydroepiandrosterone sulfate (DHEA-S) and Alzheimer's dementia in older subjects. Int J Geriatr Psychiatry 2006; 21:1065-1070. (Pubitemid 44762724)
13. Rodriguez A, Muller DC, Metter EJ, et al. Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. J Clin Endocrinol Metab 2007; 92:3568-3572. (Pubitemid 47435336)
14. Rosario E, Chang L, Stanczyk F, Pike C. Age-related testosterone depletion and the development of Alzheimer disease. JAMA 2004; 292:1431-1432. (Pubitemid 39258334)
15. Chu LW, Tam S, Lee PW, et al. Bioavailable testosterone is associated with a reduced risk of amnestic mild cognitive impairment in older men. Clin Endocrinol (Oxf) 2008; 68:589-598. The above article was the first to report an association between low bioavailable testosterone and MCI.
16. Hogervorst E, Bandelow S, Combrinck M, Smith AD. Low free testosterone is an independent risk factor of Alzheimer's disease. Exp Gerontol 2004; 39:1633-1639. (Pubitemid 39576135)
17. Moffat SD, Zonderman AB, Metter EJ, et al. Free testosterone and risk for Alzheimer's disease in older men. Neurology 2004; 62:188-193. (Pubitemid 38167123)
18. Paoletti AM, Congia S, Lello S, et al. Low androgenization index in elderly women and elderly men with Alzheimer's disease. Neurology 2004; 62:301-303. (Pubitemid 38167146)
19. Naylor JC, Hulette CM, Steffens DC, et al. Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage. J Clin Endocrinol Metab 2008; 93:3173-3178. The above article examines the use of DHEA as a marker for Alzheimer's disease.
20. Kim SB, Hill M, Kwak YT, et al. Neurosteroids: cerebrospinal fluid levels for Alzheimer's disease and vascular dementia diagnostics. J Clin Endocrinol Metab 2003; 88:5199-5206. (Pubitemid 37452716)
21. Bastianetto S, Ramassamy C, Poirier J, Quirion R. Dehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage. Brain Res Mol Brain Res 1999; 66:35-41. (Pubitemid 29148331)
22. Kurata K, Takebayashi M, Morinobu S. Yamawaki S. beta-estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate protect against N-methyl-D-aspartate-induced neurotoxicity in rat hippocampal neurons by different mechanisms. J Pharmacol Exp Ther 2004; 311:237-245. (Pubitemid 39287803)
23. Kato-Negishi M, Kawahara M. Neurosteroids block the increase in intracellular calcium level induced by Alzheimer's beta-amyloid protein in long term cultured rat hippocampal neurons. Neuropsychiatr Dis Treat 2008; 4: 209-218.
24. Moffat SD, Zonderman AB, Metter EJ, et al. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab 2002; 87:5001-5007.
25. Muller M, Aleman A, Grobbee DE, et al. Endogenous sex hormone levels and cognitive function in aging men: is there an optimal level? Neurology 2005; 64:866-871.
26. Janowsky J, Chavez B, Orwoll E. Sex steroids modify working memory. J Cogn Neurosci 2000; 12:407-414. (Pubitemid 30410281)
27. Cherrier MM, Craft S, Matsumoto AH. Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. J Androl 2003; 24:568-576. (Pubitemid 38129058)
28. Almeida OP, Waterreus A, Spry N, et al. One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology 2004; 29:1071-1081. (Pubitemid 38833535)
29. Lessov-Schlaggar CN, Reed T, Swan GE, et al. Association of sex steroid hormones with brain morphology and cognition in healthy elderly men. Neurology 2005; 65:1591-1596. (Pubitemid 41689474)
30. Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 2008; 299:39-52. Largest clinical trial of testosterone to date.
31. Lu PH, Masterman DA, Mulnard R, et al. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol 2006; 63:177-185. (Pubitemid 43261728)
32. Tan RS, Pu SJ. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Aging Male 2003; 6:13-17.
33. Cherrier MM, Matsumoto AM, Amory JK, et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology 2005; 64:2063-2068.
34. McGowan E, Eriksen J, Hutton M. A decade of modeling Alzheimer's disease in transgenic mice. Trends Genet 2006; 22:281-289.
35. Park SY, Tournell C, Sinjoanu RC, Ferreira A. Caspase-3-and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in beta-amyloid-treated hippocampal neurons. Neuroscience 2007; 144:119-127. Study that shows gonadal steroids modulate tau cleavage and cell death. (Pubitemid 44841997)
36. Pike C. Testosterone attenuates beta-amyloid toxicity in cultured hippocampal neurons. Brain Res 2001; 919:160-165. (Pubitemid 33016600)
37. Nguyen T, Yao M, Pike C. Androgens activate mitogen-activated protein kinase signaling: role in neuroprotection. J Neurochem 2005; 94:1639-1651. (Pubitemid 41324645)
38. Hammond J, Le Q, Goodyer C, et al. Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons. J Neurochem 2001; 77:1319-1326. (Pubitemid 32523685)
39. Lee SH, Heo JS, Lee MY, Han HJ. Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. J Cell Physiol 2008; 216:269-275. (Pubitemid 351813118)
40. Ahlbom E, Prins GS, Ceccatelli S. Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res 2001; 892:255-262. (Pubitemid 32141211)
41. Ramsden M, Shin T, Pike C. Androgens modulate neuronal vulnerability to kainite lesion. Neuroscience 2003; 122:573-578. (Pubitemid 37410278)
42. Azcoitia I, Sierra A, Veiga S, et al. Brain aromatase is neuroprotective. J Neurobiol 2001; 47:318-329.
43. Gouras GK, Xu H, Gross RS, et al. Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Proc Natl Acad Sci U S A 2000; 97:1202-1205. (Pubitemid 30080836)
44. Ramsden M, Nyborg A, Murphy M, et al. Androgens modulate beta-amyloid levels in the male rat brain. J Neurochem 2003; 87:1052-1055. (Pubitemid 37444579)
45. Rosario E, Carroll J, Oddo S, et al. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J Neurosci 2006; 26:13384-13389. (Pubitemid 46011649)
46. Wahjoepramono EJ, Wijaya LK, Taddei K, et al. Distinct effects of testosterone on plasma and cerebrospinal fluid amyloid-beta levels. J Alzheimers Dis 2008; 15:129-137. The above article examines the relationship between testosterone and beta amyloid in guinea pigs.
47. Ghosh S, Thakur MK. PS1 expression is downregulated by gonadal steroids in adult mouse brain. Neurochem Res 2008; 33:365-369. The above article shows that presenilin 1 expression is regulated by gonadal steroids (Pubitemid 351230436)
48. Ghosh S, Thakur MK. PS2 protein expression is upregulated by sex steroids in the cerebral cortex of aging mice. Neurochem Int 2008; 52:363-367. The above article shows that presenilin 2 expression is regulated by gonadal steroids.
49. Goodenough S, Engert S, Behl C. Testosterone stimulates rapid secretory amyloid precursor protein release from rat hypothalamic cells via the activation of the mitogen-activated protein kinase pathway. Neurosci Lett 2000; 296:49-52.
50. Choi SH, Leight SN, Lee VM, et al. Accelerated Abeta deposition in APPswe/PS1deltaE9 mice with hemizygous deletions of TTR (transthyretin). J Neurosci 2007; 27:7006-7010.
51. Quintela T, Alves CH, Goncalves I, et al. 5alpha-dihydrotestosterone upregulates transthyretin levels in mice and rat choroid plexus via an androgen receptor independent pathway. Brain Res 2008; 1229:18-26. A study that shows androgens regulate TTR expression and beta amyloid levels.
52. Yao M, Nguyen TV, Rosario ER, et al. Androgens regulate neprilysin expression: role in reducing beta-amyloid levels. J Neurochem 2008; 105:2477-2488. Novel mechanism of how androgens regulate beta amyloid levels is shown in the above article. (Pubitemid 351782277)
53. Zheng R, Shen R, Goodman OB Jr, Nanus DM. Multiple androgen response elements cooperate in androgen regulated activity of the type 1 neutral endopeptidase promoter. Mol Cell Endocrinol 2006; 259:10-21. (Pubitemid 44430115)
54. Papasozomenos S. The heat shock-induced hyperphosphorylation of tau is estrogen-independent and prevented by androgens: implications for Alzheimer disease. Proc Natl Acad Sci U S A 1997; 94:6612-6617. (Pubitemid 27281912)
55. Papasozomenos S, Papasozomenos H. The activation of heat shock transcription factor 1 is differentially regulated in the brain of estrogen- and testosterone-treated heat-shocked rats. J Alzheimers Dis 2008; 15:375-390.
56. Papasozomenos S, Shanavas A. Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3 beta but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of tau: implications for Alzheimer's disease. Proc Natl Acad Sci U S A 2002; 99:1140-1145. (Pubitemid 34136460)
57. Short RA, Bowen RL, O'Brien PC, Graff-Radford NR. Elevated gonadotropin levels in patients with Alzheimer's disease. Mayo Clin Proc 2001; 76:906-909. (Pubitemid 32825912)
58. Bowen RL, Isley JP, Atkinson RL. An association of elevated serum gonadotropin concentrations and Alzheimer disease? J Neuroendocrinol 2000; 12:351-354.
59. Hogervorst E, Combrinck M, Smith AD. Testosterone and gonadotropin levels in men with dementia. Neuro Endocrinol Lett 2003; 24:203-208. (Pubitemid 37074814)
60. Lei Z, Rao C, Kornyei J, et al. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in the brain. Endocrinology 1993; 132:2262-2270. (Pubitemid 23133280)
61. Bowen R, Smith M, Harris P, et al. Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology. J Neurosci Res 2002; 70:514-518. (Pubitemid 35222388)
62. Verdile G, Yeap BB, Clarnette RM, et al. Luteinizing hormone levels are positively correlated with plasma amyloid-beta protein levels in elderly men. J Alzheimers Dis 2008; 14:201-208. The above was the first to report a correlation between LH and plasma beta-amyloid in men. (Pubitemid 352040037)
63. Bowen R, Verdile G, Liu T, et al. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition. J Biol Chem 2004; 279:20539-20545. (Pubitemid 38623501)
64. Casadesus G, Webber K, Atwood C, et al. Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice. Biochim Biophys Acta 2006; 1762:447-452. (Pubitemid 43344306)
65. Casadesus G, Milliken E, Webber K, et al. Increases in luteinizing hormone are associated with declines in cognitive performance. Mol Cell Endocrinol 2007; 269:107-111. (Pubitemid 46483837)
66. Webber K, Perry G, Smith M, Casadesus G. The contribution of luteinizing hormone to Alzheimer disease pathogenesis. Clin Med Res 2007; 5:177-183. A review about leuprolide acetate as a therapy for Alzheimer's disease. (Pubitemid 351303232)