Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice.
Until recently, the study of hormonal influences in Alzheimer disease was limited to the role of sex steroids. Despite numerous epidemiological studies supporting a protective role for estrogen in Alzheimer disease, recent studies show that estrogen administration in elderly women increases the risk of disease. Reconciling these contradictory reports, we previously hypothesized that other hormones of the hypothalamic-pituitary-gonadal axis, such as luteinizing hormone, may be involved in the onset and development of the disease. In this regard, luteinizing hormone is elevated in Alzheimer disease and is known to modulate amyloidogenic processing of amyloid-beta protein precursor. Therefore, in this study, to evaluate the therapeutic potential of luteinizing hormone ablation, we administered a gonadotropin-releasing hormone analogue, leuprolide acetate, to an aged transgenic mouse model of Alzheimer disease (Tg 2576) and measured cognitive Y-maze performance and amyloid-beta deposition after 3 months of treatment. Our data indicate that luteinizing hormone ablation significantly attenuated cognitive decline and decreased amyloid-beta deposition as compared to placebo-treated animals. Importantly, leuprolide acetate-mediated reduction of amyloid-beta correlated with improved cognition. Since both cognitive loss and amyloid-beta deposition are features of Alzheimer disease, leuprolide acetate treatment may prove to be a useful therapeutic strategy for this disease.
Casadesus
Gemma
G
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Webber
Kate M
KM
Atwood
Craig S
CS
Pappolla
Miguel A
MA
Perry
George
G
Bowen
Richard L
RL
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D016729:Leuprolide / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000819:agonists / Q000502:physiology*; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D020033:Protein Isoforms; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D016729:Leuprolide