Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia -
School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia.
Panminerva Med. 2020 Sep;62(3):155-163. doi: 10.23736/S0031-0808.20.03879-3. Epub 2020 Mar 23.
Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) are two of the most commonly occurring diseases worldwide, especially among the elderly population. In particular, the increased prevalence of AD has imposed tremendous psychological and financial burdens on society. Growing evidence suggests both AD and T2D share many similar pathological traits. AD is characterized as a metabolic disorder whereby the glucose metabolism in the brain is impaired. This closely resembles the state of insulin resistance in T2D. Insulin resistance of the brain has been heavily implicated two prominent pathological features of AD, Aβ plaques and neurofibrillary tangles. Brain insulin resistance is known to elicit a positive feed-forward loop towards the formation of AD pathology in which they affect each other in a synergistic manner. Other physiological traits shared between the two diseases include inflammation, oxidative stress and autophagic dysfunction, which are also closely associated with brain insulin resistance. In this review and depending on these underlying pathways that link these two diseases, we have discussed the potential therapeutic implications of AD. By expanding our knowledge of the overlapping pathophysiology involved, we hope to provide scientific basis to the discovery of novel therapeutic strategies to improve the clinical outcomes of AD in terms of diagnosis and treatment.
阿尔茨海默病(AD)和 2 型糖尿病(T2D)是全球最常见的两种疾病,尤其是在老年人群中。特别是 AD 的发病率不断上升,给社会带来了巨大的心理和经济负担。越来越多的证据表明,AD 和 T2D 具有许多相似的病理特征。AD 被认为是一种代谢紊乱,大脑中的葡萄糖代谢受到损害。这与 T2D 中的胰岛素抵抗状态非常相似。大脑胰岛素抵抗与 AD 的两个突出病理特征 Aβ斑块和神经原纤维缠结密切相关。众所周知,大脑胰岛素抵抗会引发 AD 病理形成的正反馈循环,它们以协同方式相互影响。这两种疾病之间还存在其他共同的生理特征,包括炎症、氧化应激和自噬功能障碍,这些特征也与大脑胰岛素抵抗密切相关。在这篇综述中,根据这些将两种疾病联系起来的潜在途径,我们讨论了 AD 的潜在治疗意义。通过扩展我们对这些重叠的病理生理学的认识,我们希望为发现改善 AD 临床诊断和治疗效果的新治疗策略提供科学依据。