Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, 06132 Perugia, Italy.
Int J Mol Sci. 2017 Dec 9;18(12):2672. doi: 10.3390/ijms18122672.
Alzheimer's disease (AD) represents the most common form of dementia among older age subjects, and despite decades of studies, the underlying mechanisms remain unresolved. The definition of AD has changed over the past 100 years, and while early-onset AD is commonly related to genetic mutations, late-onset AD is more likely due to a gradual accumulation of age-related modifications. "Normal brain aging" and AD may represent different pathways of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes (ARCs) affecting the brain may be considered as biologic manifestations of increasing entropy, a measure of disorder. Late-onset AD may be regarded as the final effect of a reduced energy production, due to exhausted mitochondria, and an increased entropy in the brain. This unique trajectory enables a bioenergetics-centered strategy targeting disease-stage specific profile of brain metabolism for disease prevention and treatment.
阿尔茨海默病（AD）是老年人中最常见的痴呆症形式，尽管经过了几十年的研究，但潜在机制仍未得到解决。AD 的定义在过去 100 年中发生了变化，虽然早发性 AD 通常与遗传突变有关，但晚发性 AD 更可能是由于年龄相关的逐渐积累所致。“正常大脑衰老”和 AD 可能代表了大脑结构和脑功能成功或失败适应能力的不同途径。影响大脑的细胞衰老和与年龄相关的变化（ARCs）可被视为熵增加的生物学表现，熵是衡量无序程度的指标。晚发性 AD 可能被视为由于线粒体耗竭导致能量产生减少以及大脑熵增加的最终结果。这种独特的轨迹为以生物能量为中心的策略提供了可能性，该策略针对疾病阶段的大脑代谢特定特征，以进行疾病的预防和治疗。
