Alzheimer Disease: Yue Y

Zhang B, Dong Y, Zhang G, Moir RD, Xia W, Yue Y, Tian M, Culley DJ, Crosby G, Tanzi RE, Xie Z. · Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129-2060, USA. · J Biol Chem. · Pubmed #18326038 links to  free full text

Abstract: Perioperative factors including hypoxia, hypocapnia, and certain anesthetics have been suggested to contribute to Alzheimer disease (AD) neuropathogenesis. Desflurane is one of the most commonly used inhalation anesthetics. However, the effects of desflurane on AD neuropathogenesis have not been previously determined. Here, we set out to assess the effects of desflurane and hypoxia on caspase activation, amyloid precursor protein (APP) processing, and amyloid beta-protein (Abeta) generation in H4 human neuroglioma cells (H4 naïve cells) as well as those overexpressing APP (H4-APP cells). Neither 12% desflurane nor hypoxia (18% O(2)) alone affected caspase-3 activation, APP processing, and Abeta generation. However, treatment with a combination of 12% desflurane and hypoxia (18% O(2)) (desflurane/hypoxia) for 6 h induced caspase-3 activation, altered APP processing, and increased Abeta generation in H4-APP cells. Desflurane/hypoxia also increased levels of beta-site APP-cleaving enzyme in H4-APP cells. In addition, desflurane/hypoxia-induced Abeta generation could be reduced by the broad caspase inhibitor benzyloxycarbonyl-VAD. Finally, the Abeta aggregation inhibitor clioquinol and gamma-secretase inhibitor L-685,458 attenuated caspase-3 activation induced by desflurane/hypoxia. In summary, desflurane can induce Abeta production and caspase activation, but only in the presence of hypoxia. Pending in vivo confirmation, these data may have profound implications for anesthesia care in elderly patients, and especially those with AD.

Yue Y, Hu L, Tian QJ, Jiang JM, Dong YL, Jin ZY, Cheng YH, Hong X, Ge QS, Zuo PP. · School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Science, Chinese Academy of Medical Sciences, Beijing, China. · Acta Pharmacol Sin. · Pubmed #17640473 links to  free full text

Abstract: AIM: To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E (apoE) gene epsilon3 or epsilon4. METHODS: Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE epsilon4 and epsilon3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. RESULTS: Analysis with the apoE epsilon4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE epsilon4 carriers in the HRT group, compared with the control group. For the apoE epsilon3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. CONCLUSION: This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE epsilon3 carriers.

Hu L, Yue Y, Zuo PP, Jin ZY, Feng F, You H, Li ML, Ge QS. · Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730. · Chin Med Sci J. · Pubmed #17249194 No free full text.

Abstract: OBJECTIVE: To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopausal women in hormone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy (MRS) parameters. METHODS: A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [estradiol (E2) 0.5-1.0 mg and progesterone 0.5-2.0 mg, once a day] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay (ELISA). The gene types of apolipoprotein E (ApoE) were measured by polymerase chain reaction, and the subjects with susceptible genes (ApoE epsilon3/epsilon4) of Alzheimer's disease (AD) were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging (MRI), and results in two groups were analyzed by statistical method. RESULTS: Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher (P < 0.05) except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups. The results of hippocampus MRI for the subjects with susceptible genes ApoE epsilon3/epsilon4 (HRT group 14 cases, control group 11 cases) showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group (0.406 +/- 0.028) was significantly higher than control group (0.369 +/- 0.031, P < 0.05). The results of 1H MRS for the subjects with susceptible genes ApoE epsilon3/epsilon4 (HRT group 12 cases, control group 11 cases) showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group (1.54 +/- 0.08) were significantly higher than control group (1.45 +/- 0.13, P < 0.05). CONCLUSIONS: For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE epsilon3/epsilon4 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.