Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life.
Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life.
复制标题
早年脑灌注通常较高的大脑区域在晚年可能更容易受到β淀粉样蛋白沉积的影响。
DOI：
10.1016/j.cccb.2020.100001
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Brickman,AdamM
中科院分区：
文献类型：
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作者：
Meier,IreneB;Lao,PatrickJ;Gietl,Anton;Vorburger,RobertS;Gutierrez,José;Holland,ChristopherM;Guttmann,CharlesRG;Meier,DominikS;Buck,Alfred;Nitsch,RogerM;Hock,Christoph;Unschuld,PaulG;Brickman,AdamM
背景淀粉样蛋白级联假说描述了阿尔茨海默病（AD）病理变化的刻板进展，其开始于β淀粉样蛋白沉积，但没有解决淀粉样蛋白沉积的原因。在早期生活中具有相对较高的神经元活动、代谢需求和活性氧物质产生的脑区域在以后的生活中可能具有较高的β淀粉样蛋白沉积。本研究的目的是调查早期生活模式的灌注和晚期生活模式的淀粉样蛋白沉积，以确定在何种程度上正常脑灌注倾向于特定区域未来β淀粉样蛋白沉积。（年龄：56-87岁; 44%的女性）接受了用[11 C]PiB进行的正电子发射断层扫描（PET）成像，以测量淀粉样蛋白负荷。对47例接受单光子发射计算机断层扫描（SPECT）成像的健康年轻人（年龄：22-49; 47%）的脑灌注图进行平均，以创建代表年轻健康成人的标准模板。在Hammers图谱的31个皮质区域中研究了灌注和淀粉样蛋白测量。我们研究了正常灌注模式和淀粉样蛋白病理生理学之间的空间关系。（颞叶<顶叶<额叶<扣带回<枕叶; F（4，26）= 7.8，p = 0.0003），健康成年人与淀粉样蛋白负荷增加的模式并不完全相同，（颞叶<枕叶<额叶<顶叶<枕/扣带回; F（4，26）= 5.0，p = 0.004）。然而，研究皮质叶内的亚区提供了AD中淀粉样蛋白进展的分级标准灌注模式和预期塔尔分期之间的一致性（Spearmanr= 0.39，p = 0.03）.结论我们的研究结果表明，正常情况下灌注量较大的脑区可能在晚年更容易发生淀粉样蛋白沉积，这可能是由于代谢需求较高，以及相关的氧化应激和炎症水平。
BackgroundThe amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer's disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition.Materials and MethodsOne hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology.ResultsThe pattern of increasing perfusion (temporal lobe<parietal lobe<frontal lobe<insula/cingulate gyrus<occipital lobe; F(4,26)=7.8,p= 0.0003) in young, healthy adults was not exactly identical to but approximated the pattern of increasing amyloid burden (temporal lobe<occipital lobe<frontal lobe<parietal lobe<insula/cingulate gyrus; F(4,26)=5.0,p= 0.004) in older adults. However, investigating subregions within cortical lobes provided consistent agreement between ranked normative perfusion patterns and expected Thal staging of amyloid progression in AD (Spearmanr= 0.39,p= 0.03).ConclusionOur findings suggest that brain areas with normatively greater perfusion may be more susceptible to amyloid deposition in later life, possibly due to higher metabolic demand, and associated levels of oxidative stress and inflammation.