Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study.
Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study.
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DOI：
10.1001/jamaneurol.2013.4544
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发表时间：
2014-01
期刊：
影响因子：
29
通讯作者：
Reiman, Eric M.
中科院分区：
文献类型：
--
作者：
Dean, Douglas C., III;Jerskey, Beth A.;Chen, Kewei;Protas, Hillary;Thiyyagura, Pradeep;Roontiva, Auttawat;O'Muircheartaigh, Jonathan;Dirks, Holly;Waskiewicz, Nicole;Lehman, Katie;Siniard, Ashley L.;Turk, Mari N.;Hua, Xue;Madsen, Sarah K.;Thompson, Paul M.;Fleisher, Adam S.;Huentelman, Matthew J.;Deoni, Sean C. L.;Reiman, Eric M.
越来越多的证据表明，大脑结构的改变可能比阿尔茨海默病的明显认知障碍早几十年。这些改变的早期检测对于预防性治疗疗法的开发和评估具有内在价值。比较载脂蛋白E（APOE）ε 4等位基因（晚发性AD的主要易感基因）携带者和非携带者的健康婴儿的白色物质髓鞘水分数（MWF）和灰质体积（GMV）的磁共振成像测量值。在一个学术研究成像中心对162名健康的婴儿进行了安静的磁共振成像，这些婴儿通常是2至25个月大的婴儿，没有阿尔茨海默病或其他神经或精神疾病的家族史。在APOE ε 4携带者和非携带者组中比较横断面测量。对162名2~25个月大的睡眠婴儿（60名ε 4携带者和102名非携带者）的白色物质MWF进行了比较。在59名6~25个月大的婴儿（23名ε 4携带者和36名非携带者）中比较了灰质体积，这些婴儿在扫描过程中保持睡眠。携带者和非携带者组在年龄、妊娠期、出生体重、性别比、母亲年龄、教育和社会经济地位方面相匹配。自动算法比较了携带者和非携带者群体中的局部白色物质MWF和GMV，并描述了它们与年龄的关系。ε 4携带者的楔前叶、后/中扣带、外侧颞叶和内侧枕颞叶区域的MWF和GMV测量值低于非携带者，这些区域优先受AD影响，而在广泛的额叶区域的MWF和GMV测量值高于非携带者，并且在2至6个月大的婴儿亚组中测量值也具有显著性（多重比较校正后，MWF差异P <0.05;多重比较未校正的GMV差异P <0.001）。婴儿ε 4携带者在后白色区的MWF与年龄之间的关系也减弱。虽然我们的发现应该被认为是初步的，但这项研究表明了与AD遗传易感性相关的一些最早的大脑变化。它提出了关于APOE在正常人脑发育中的作用的新问题，这些过程与随后的AD病理学相关的程度，以及它们是否可以被AD预防疗法靶向。
Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies.
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影响因子：
5.7
作者：
Jenkinson, M;Bannister, P;Smith, S
通讯作者：
Smith, S
影响因子：
2.4
作者：
Ihle, Andreas;Bunce, David;Kliegel, Matthias
通讯作者：
Kliegel, Matthias
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2.5
作者：
MacKay, A;Laule, C;M채dler, B
通讯作者：
M채dler, B
影响因子：
15.9
作者：
Ewers M;Sperling RA;Klunk WE;Weiner MW;Hampel H
通讯作者：
Hampel H
影响因子：
3.2
作者：
Buckner, RL;Snyder, AZ;Morris, JC
通讯作者：
Morris, JC