Monacelli Fiammetta, Borghi Roberta, Cammarata Sergio, Nencioni Alessio, Piccini Alessandra, Tabaton Massimo, Odetti Patrizio
Department of Internal Medicine and Medical Specialties (DiMI), Section of Geriatrics. University of Genova, Genova, Italy.
Memory Clinic of Neurology Unit, Galliera Hospital, Genova, Italy.
J Alzheimers Dis. 2015;45(1):89-95. doi: 10.3233/JAD-142511.
Autopsy studies have indicated brain accumulation of amyloid-β peptides as a common pathogenetic hallmark of amnestic cognitive impairment (aMCI) and overt Alzheimer's disease (AD). The pathogenesis of AD is still debated but recent reports have even designated AD as type III diabetes. This study aims to assess plasma levels of malondialdehyde, pentosidine, and insulin resistance in a group of aMCI patients, AD subjects, and age- and gender-matched controls, to confirm, beyond the accumulation of amyloid-β, the presence of a metabolic disorder, as a causative/contributive factor for AD. Patients were recruited and diagnosed as aMCI (n = 180), AD (n = 84), and age- and gender-matched controls (n = 62) at three different Italian memory clinics. Plasma insulin and glucose, plasma pentosidine and malondialdehyde (MDA), HOMA-IR and QUICKI score for insulin sensitivities indexes were collected at the basal visit. Plasma MDA levels were higher in the aMCI group who converted to AD compared to controls, stable aMCI subjects, and AD subjects (p < 0.01) respectively, while plasma pentosidine was higher compared to controls. The aMCI group showed a significant correlation between HOMA-IR, QUICKI, insulin, and MDA (p < 0.02). aMCI might be considered the early biochemical active disease stage where glycoxidation, hyperinsulinemia, and pro-amyloidogenic status are at the highest rate while overt AD might indicate the glycoxidative cascade dwindling, ending a process possibly started two decades earlier.
尸检研究表明，β淀粉样肽在大脑中的积累是遗忘型认知障碍（aMCI）和显性阿尔茨海默病（AD）常见的发病机制标志。AD的发病机制仍存在争议，但最近的报告甚至将AD称为III型糖尿病。本研究旨在评估一组aMCI患者、AD患者以及年龄和性别匹配的对照组的血浆丙二醛、戊糖苷和胰岛素抵抗水平，以证实除了β淀粉样蛋白的积累外，是否存在代谢紊乱，作为AD的致病/促成因素。在意大利的三家不同记忆诊所招募并诊断了患者，分别为aMCI组（n = 180）、AD组（n = 84）和年龄和性别匹配的对照组（n = 62）。在基础访视时收集血浆胰岛素和葡萄糖、血浆戊糖苷和丙二醛（MDA）、胰岛素敏感性指数的HOMA-IR和QUICKI评分。与对照组、稳定的aMCI受试者和AD受试者相比，转化为AD的aMCI组血浆MDA水平分别更高（p < 0.01），而血浆戊糖苷水平高于对照组。aMCI组的HOMA-IR、QUICKI、胰岛素和MDA之间存在显著相关性（p < 0.02）。aMCI可能被认为是早期生化活跃疾病阶段，此时糖氧化、高胰岛素血症和淀粉样蛋白生成前状态处于最高水平，而显性AD可能表明糖氧化级联反应减弱，结束了一个可能在二十年前就开始的过程。
