NanoBio Laboratory, Department of Chemical Engineering, Widener University, Chester, PA 19013, USA.
Med Hypotheses. 2012 Apr;78(4):494-6. doi: 10.1016/j.mehy.2012.01.015. Epub 2012 Jan 28.
Alzheimer's disease (AD) is a complex, multifactorial progressive neurodegenerative disease. Pathologically, AD is characterized by extracellular deposits of amyloid beta (Aβ) protein and intracellular accumulation of neurofibrillary tangles (NFTs) of tau. The central role of Aβ protein in the AD etiology is well-established, and its increased deposition in AD brain is attributed to its decreased clearance from the brain. It is noteworthy that apolipoprotein E (ApoE), the most significant risk factor for late-onset AD, has been shown to play a vital role in brain Aβ clearance and the ability of ApoE to do this depends mainly upon its lipidation status. Thus, lower ApoE lipidation status leading to decreased Aβ clearance may underlie the increased Aβ deposition observed in AD brain. In addition to the pathophysiological Aβ deposits, AD is also characterized by certain metabolic changes. Among them, decreased cerebral glucose metabolism is one of the distinct characteristics of AD brain and is also observed in patients with Mild Cognitive Impairment (MCI) who subsequently develop AD. Thus, decreased cerebral glucose metabolism is an early event in AD pathology and may precede the neuropathological Aβ deposition associated with AD. In this context, we hypothesize here that the decreased glucose metabolism in pre-AD and early AD stages, may lead to lower ApoE lipidation status, which in turn may lead to decreased clearance and hence, increased deposition of Aβ protein in AD brain.
阿尔茨海默病（AD）是一种复杂的、多因素的进行性神经退行性疾病。从病理学上看，AD 的特征是细胞外淀粉样β（Aβ）蛋白沉积和细胞内 tau 神经原纤维缠结（NFTs）的积累。Aβ 蛋白在 AD 发病机制中的核心作用已得到充分证实，其在 AD 大脑中的沉积增加归因于其从大脑中的清除减少。值得注意的是，载脂蛋白 E（ApoE）是晚发性 AD 的最重要危险因素，它在大脑 Aβ 清除中发挥着至关重要的作用，而 ApoE 发挥这一作用主要取决于其脂质化状态。因此，导致 Aβ 清除减少的 ApoE 脂质化状态降低可能是 AD 大脑中观察到的 Aβ 沉积增加的基础。除了病理生理学上的 Aβ 沉积外，AD 还表现出某些代谢变化。其中，脑葡萄糖代谢降低是 AD 大脑的一个明显特征，也存在于随后发展为 AD 的轻度认知障碍（MCI）患者中。因此，脑葡萄糖代谢降低是 AD 病理的早期事件，可能早于与 AD 相关的神经病理学 Aβ 沉积。在这种情况下，我们在这里假设 AD 前和早期阶段的葡萄糖代谢降低，可能导致 ApoE 脂质化状态降低，进而导致 Aβ 蛋白清除减少，从而导致 AD 大脑中 Aβ 蛋白沉积增加。
