Down-regulation of serum gonadotropins but not estrogen replacement improves cognition in aged-ovariectomized 3xTg AD female mice (pages 115–125)
Russell Palm, Jaewon Chang, Jeffrey Blair, Yoelvis Garcia-Mesa, Hyoung-gon Lee, Rudy J. Castellani, Mark A. Smith, Xiongwei Zhu and Gemma Casadesus
Version of Record online: 2 APR 2014 | DOI: 10.1111/jnc.12706
In the aged triple transgenic Alzheimer's disease (AD) mouse model (3xAD-Tg), estrogen replacement after ovariectomy does not improve cognitive function, increases phosphorylated Tau levels and decreases inhibition of GSK3 beta. Luprolide acetate rescues ovariectomy-dependent cognitive function, increases signaling events associated with synaptic plasticity including GSK3 beta inhibition, but does not alter AD pathology. In the human AD female brain, luteinizing hormone (LH) mRNA levels are reduced. In the 3XAD-tg model, brain LH protein levels are reduced by ovariectomy and normalized by leuprolide acetate treatment. These treatment-dependent normalization of LH positively correlates with markers of neuroplasticity and cognitive improvement.