Lehmann Donald J, Elshorbagy Amany, Hurley Michael J
Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, UK.
Department of Pharmacology, University of Oxford, Oxford, UK.
J Alzheimers Dis. 2023;95(4):1371-1382. doi: 10.3233/JAD-230295.
Sporadic Alzheimer's disease (AD) is a complex, multifactorial disease. We should therefore expect to find many factors involved in its causation. The known neuropathology seen at autopsy in patients dying with AD is not consistently seen in all patients with AD and is sometimes seen in patients without dementia. This suggests that patients follow different paths to AD, with different people having slightly different combinations of predisposing physical, chemical and biologic risk factors, and varying neuropathology. This review summarizes what is known of the biologic and chemical predisposing factors and features in AD. We postulate that, underlying the neuropathology of AD is a progressive failure of neurons, with advancing age or other morbidity, to rid themselves of entropy, i.e., the disordered state resulting from brain metabolism. Understanding the diverse causes of AD may allow the development of new therapies targeted at blocking the paths that lead to dementia in each subset of patients.
散发性阿尔茨海默病（AD）是一种复杂的多因素疾病。因此，我们应该预期会发现许多导致该病的因素。在死于AD的患者尸检中所见的已知神经病理学特征，并非在所有AD患者中都一致出现，有时在无痴呆的患者中也会出现。这表明患者患AD的途径不同，不同的人具有略有不同的身体、化学和生物易患风险因素组合，以及不同的神经病理学特征。本综述总结了AD中已知的生物和化学易患因素及特征。我们推测，AD神经病理学的基础是随着年龄增长或其他疾病的发生，神经元逐渐无法消除熵，即由脑代谢产生的无序状态。了解AD的多种病因可能有助于开发新的治疗方法，针对阻断导致各亚组患者痴呆的途径。
