Díaz-Ruiz C, Wang J, Ksiezak-Reding H, Ho L, Qian X, Humala N, Thomas S, Martínez-Martín P, Pasinetti G M
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY10029, USA.
Cardiovasc Psychiatry Neurol. 2009;2009:107286. doi: 10.1155/2009/107286. Epub 2009 Sep 17.
Epidemiological evidence suggests that hypertension may accelerate the onset and progression of Alzheimer's disease (AD). In this study, we explored the role of hypertension in the neurodegenerative changes associated with Abeta and tau aggregation. We induced hypertension in APP(swe) Tg2576 and P301L-tauTg mouse models. In Tg2576 mice, experimental hypertension was associated with a significant increase of the accumulation of Amyloid-beta (Abeta) peptides in brain tissue and a significant reduction of Abeta peptides in serum (P < .05). These results indicate that hypertension may promote AD-type Abeta neuropathology in Tg2576. In P301L-tauTg mice we found that the presence of hypertension was significantly associated with aggravated motor function assessed by hindlimb extension test (P = .01). These results suggest that hypertension may play a role in accelerating the progression of motor dysfunction associated with tau-related alterations. Our studies suggest that the management of blood pressure (BP) may alleviate AD-type Abeta neuropathology and neurological disorders associated with abnormal tau metabolism.
流行病学证据表明,高血压可能会加速阿尔茨海默病(AD)的发病和进展。在本研究中,我们探讨了高血压在与β淀粉样蛋白(Aβ)和tau蛋白聚集相关的神经退行性变化中的作用。我们在APP(swe)Tg2576和P301L-tauTg小鼠模型中诱导高血压。在Tg2576小鼠中,实验性高血压与脑组织中淀粉样β蛋白(Aβ)肽积累的显著增加以及血清中Aβ肽的显著减少相关(P < 0.05)。这些结果表明,高血压可能促进Tg2576小鼠中AD型Aβ神经病理学改变。在P301L-tauTg小鼠中,我们发现高血压的存在与通过后肢伸展试验评估的运动功能加重显著相关(P = 0.01)。这些结果表明,高血压可能在加速与tau相关改变的运动功能障碍进展中起作用。我们的研究表明,血压管理可能会减轻AD型Aβ神经病理学改变以及与异常tau代谢相关的神经疾病。