Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.
Brain Res Bull. 2012 Nov 1;89(3-4):144-9. doi: 10.1016/j.brainresbull.2012.08.003. Epub 2012 Aug 18.
The past decade has shed new light on the etiology of Alzheimer's disease (AD), which is the consequence of interactions between numerous lesions. There is a growing body of evidence that the most beneficial effects of treatment might only be achieved in the preclinical stage of dementia, prior to the immense hallmarks of neurodegeneration. In view of this, several studies have focused on mild cognitive impairment (MCI) as a state, which represents a less severe form of the neuropathological process. However, early treatment interventions initiated in MCI have failed to slow down progression of the disease. Thus, great effort has been made to indicate modifiable risk factors for MCI. Consistent with the role of vascular malfunction in AD, this approach has shown the predictive value of the metabolic syndrome (MetS), which is a multidimensional entity and includes visceral obesity, dyslipidemia, hyperglycemia and hypertension. Despite the positive results of several epidemiological studies, the exact mechanisms underlying the connection between MetS and AD remain uncertain and various theories are being assessed. MetS, similarly to AD, has been attributed to a low-grade chronic inflammation. There is a general consensus that the aberrant inflammatory response underlying MetS may arise from a deregulation of the endocrine homeostasis of adipose tissue. Hence, it might be assumed that the subclinical inflammation of adipose tissue may interact with the impaired central inflammatory response, leading to neurodegeneration. This article reviews the role of low-grade inflammation of adipose tissue in the pathophysiology of cognitive impairment and translates several considerable and unexplored findings from studies focused on subjects with MetS and animal models mimicking the phenotype of MetS into the etiology of AD.
过去十年，阿尔茨海默病（AD）的病因学研究有了新的进展，其是众多病变相互作用的结果。越来越多的证据表明，治疗的最有益效果可能仅在痴呆的临床前阶段实现，即在神经退行性病变的巨大标志之前。有鉴于此，一些研究集中在轻度认知障碍（MCI）作为一种状态，它代表了神经病理过程的一种不太严重的形式。然而，在 MCI 中启动的早期治疗干预措施未能减缓疾病的进展。因此，人们付出了巨大的努力来确定 MCI 的可改变风险因素。与血管功能障碍在 AD 中的作用一致，这种方法显示了代谢综合征（MetS）的预测价值，代谢综合征是一种多维实体，包括内脏肥胖、血脂异常、高血糖和高血压。尽管几项流行病学研究取得了积极的结果，但 MetS 与 AD 之间联系的确切机制仍不确定，正在评估各种理论。MetS 与 AD 一样，归因于低度慢性炎症。人们普遍认为，MetS 异常炎症反应可能源于脂肪组织内分泌稳态的失调。因此，可以假设脂肪组织的亚临床炎症可能与受损的中枢炎症反应相互作用，导致神经退行性病变。本文综述了脂肪组织低度炎症在认知障碍病理生理学中的作用，并将来自关注 MetS 患者和模拟 MetS 表型的动物模型的研究中的几个相当重要且尚未探索的发现转化为 AD 的病因。
