White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network.
White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network.
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DOI：
10.1002/ana.24647
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发表时间：
2016-06
影响因子：
11.2
通讯作者：
Dominantly Inherited Alzheimer Network
中科院分区：
文献类型：
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作者：
Lee S;Viqar F;Zimmerman ME;Narkhede A;Tosto G;Benzinger TL;Marcus DS;Fagan AM;Goate A;Fox NC;Cairns NJ;Holtzman DM;Buckles V;Ghetti B;McDade E;Martins RN;Saykin AJ;Masters CL;Ringman JM;Ryan NS;Förster S;Laske C;Schofield PR;Sperling RA;Salloway S;Correia S;Jack C Jr;Weiner M;Bateman RJ;Morris JC;Mayeux R;Brickman AM;Dominantly Inherited Alzheimer Network
白质高信号 (WMH) 是磁共振成像 (MRI) 扫描中信号增加的区域，最常反映小血管脑血管疾病。 Increased WMH volume is associated with risk and progression of Alzheimer’s disease(AD).这些观察结果通常被解释为证据，表明血管异常对症状表现起着附加的、独立的作用，但不是 AD 的核心特征。我们检查了症状前 PSEN1、PSEN2 和 APP 突变携带者中 WMH 的严重程度和分布，以确定 WMH 在基因决定的 AD 个体中表现的程度。该研究由来自显性遗传性阿尔茨海默病网络的参与者（n=299，年龄=39.03±10.13）组成，其中 184 名（61.5%）患有导致 AD 的突变，以及 115 名（38.5%）非携带者对照一级亲属。我们通过从参与者的年龄中减去受影响父母的症状出现年龄来计算预计症状出现的估计年数（EYO）。 Baseline MRI data were analyzed for total and regional WMH. Mixed effects piecewise linear regression was used to examine WMH differences between carriers and non-carriers with respect to EYO. Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years prior to expected symptom onset.顶叶和枕叶的影响最为显着，早在预计发病前 22 年就显示出不同的影响。 Autosomal dominant AD is associated with increased WMH well before expected symptom onset.研究结果表明，WMH 可能是 AD 的核心特征、潜在的治疗靶点以及应纳入该疾病致病模型的因素。
White matter hyperintensities(WMH) are areas of increased signal on magnetic resonance imaging(MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer’s disease(AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically-determined to develop AD. The study comprised participants(n=299, age=39.03±10.13) from the Dominantly Inherited Alzheimer Network, including 184(61.5%) with a mutation that results in AD and 115(38.5%) first-degree relatives who were non-carrier controls. We calculated the estimated years from expected symptom onset(EYO) by subtracting the affected parent’s symptom onset age from the participant’s age. Baseline MRI data were analyzed for total and regional WMH. Mixed effects piecewise linear regression was used to examine WMH differences between carriers and non-carriers with respect to EYO. Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years prior to expected symptom onset. The effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years prior to estimated onset. Autosomal dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMH are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease.