Department of Medicine, University of California, 2069 Filbert Street, San Francisco, CA 94123, USA.
Int J Mol Sci. 2024 Mar 20;25(6):3524. doi: 10.3390/ijms25063524.
There are two generic approaches to curing any medical condition. The first one treats every patient for all the known possible causes that contribute to pathogenesis; the second one individualizes potentially curative therapy by only identifying in each separate patient the components of pathogenesis that are actually operative and treating those. This article adopts the second approach for formulating a cure for Alzheimer's dementia (AD). The components of AD's pathogenesis are, in alphabetical order, as follows: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree to which its prevalence is higher in patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did because the former group is the pool of patients in which future AD may develop. Only addressing the components that are present in a particular individual potentially is a curative strategy. Published data indicate that curative therapy requires the number of such components that are addressed to be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit these tracts.
有两种通用的方法可以治愈任何医学病症。第一种方法针对所有已知的可能导致发病机制的病因,对所有患者进行治疗;第二种方法通过仅识别每个单独患者中实际起作用的发病机制成分,并对这些成分进行治疗,从而实现个体化的潜在治疗方法。本文采用第二种方法来制定阿尔茨海默病(AD)的治疗方法。AD 的发病机制成分按字母顺序排列如下:昼夜节律紊乱、抑郁、糖尿病和胰岛素抵抗、血脂异常、高血压、炎症、代谢综合征、线粒体功能障碍、营养缺乏、TGF-β 缺乏、体重过轻、血管异常和 Wnt/β-连环蛋白缺乏。对于每个成分,都描述了数据,表明在没有恢复正常认知的轻度认知障碍(MCI)患者中,其患病率高于那些恢复正常认知的患者,因为前者是未来可能发展为 AD 的患者群体。仅针对特定个体存在的成分进行治疗是一种有治愈潜力的策略。已发表的数据表明,治愈疗法需要解决的这些成分的数量≥3。尽管无法直接解决结构性脑变化,但受损的神经束是由许多可逆转的因果因素引起的,因此纠正这些因素将有益于这些神经束。