Koppel Jeremy, Jimenez Heidy, Adrien Leslie, Greenwald Blaine S, Marambaud Philippe, Cinamon Ezra, Davies Peter
The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute of Medical Research, Northwell Health, Manhasset, NY, USA.
The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
Alzheimers Dement (N Y). 2016 Jun 21;2(2):121-130. doi: 10.1016/j.trci.2016.05.003. eCollection 2016 Jun.
The use of antipsychotic medications in Alzheimer's disease has been associated with an increased risk of mortality in clinical trials. However, an older postmortem literature suggests that those with schizophrenia treated in an era of exclusively conventional antipsychotic medications had a surprisingly low incidence of tau pathology. No previously published studies have investigated the impact of conventional antipsychotic exposure on tau outcomes in a tau mouse model of AD.
In two experiments, transgenic rTg (tauP301L) 4510 tau mice were treated with either haloperidol or vehicle and phosphotau epitopes were quantified using high-sensitivity tau ELISA.
After treatments of 2 and 6 week's duration, mice treated with haloperidol evidenced a significant reduction in tau phosphorylation associated with an inactivation of the tau kinase AMPK.
The data suggest that D2 receptor blockade reduces tau phosphorylation in vivo. Future studies are necessary to investigate the impact of this reduction on tau neuropathology.
在临床试验中，阿尔茨海默病患者使用抗精神病药物与死亡风险增加有关。然而，较早的尸检文献表明，在仅使用传统抗精神病药物治疗的时代，精神分裂症患者的tau病理发生率出奇地低。以前没有发表的研究调查过在阿尔茨海默病的tau小鼠模型中，传统抗精神病药物暴露对tau结果的影响。
在两项实验中，用氟哌啶醇或赋形剂处理转基因rTg（tauP301L）4510 tau小鼠，并使用高灵敏度tau ELISA对磷酸化tau表位进行定量。
在持续2周和6周的治疗后，用氟哌啶醇治疗的小鼠显示tau磷酸化显著降低，这与tau激酶AMPK的失活有关。
数据表明，D2受体阻断可在体内降低tau磷酸化。有必要进行进一步研究以调查这种降低对tau神经病理学的影响。
