APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging.
APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging.
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DOI：
10.1001/archneurol.2009.913
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发表时间：
2010-01
影响因子：
--
通讯作者：
Resnick, Susan M.
中科院分区：
文献类型：
--
作者：
Thambisetty, Madhav;Beason-Held, Lori;An, Yang;Kraut, Michael A.;Resnick, Susan M.
我们使用正电子发射断层扫描技术研究了巴尔的摩老龄化纵向研究中ε4携带者和非携带者在非痴呆老年人局部脑血流量纵向变化上的差异。我们的主要目的是检查载脂蛋白Eε4携带者是否存在区域性的局部脑血流纵向变化，这些变化可能与其作为阿尔茨海默病(AD)遗传风险因素的公认角色有关。使用[15O]水正电子发射计算机断层扫描和基于体素的分析，我们比较了55岁以上非痴呆载脂蛋白Eε4携带者(N=29)和非携带者(N=65)8年间局部脑血流的变化。收集了所有参与者的一系列神经心理学数据。ε-4携带者与非携带者rCBF的纵向变化存在广泛差异。ε-4携带者的rCBF下降幅度较大。这些差异在额叶、顶叶和颞叶皮质中观察到。受影响的大脑区域是那些特别容易受到AD病理影响的区域。在研究过程中，ε4携带者和非携带者都没有被诊断为痴呆症或轻度认知障碍。我们的研究结果表明，载脂蛋白Eε4介导的AD风险与痴呆发病前的rCBF随时间的广泛下降有关。APOEε4患者脑功能下降速度加快可能是他们AD风险增加和发病年龄较低的原因之一。
We used positron emission tomography (PET) to study differences in longitudinal changes in regional cerebral blood flow (rCBF) between APOE ε4 carriers and non-carriers in non-demented older adults from the Baltimore Longitudinal Study of Aging (BLSA). Our main aim was to examine whether there are regionally specific longitudinal changes in rCBF in APOE ε4 carriers that might be related to its well-established role as a genetic risk factor for Alzheimer’s disease (AD). Using [15O]water PET and voxel-based analysis, we compared changes in rCBF over an 8-year period between non-demented APOE ε4 carriers (N=29) and non-carriers (N=65) over 55 years of age. Serial neuropsychological data were collected for all participants. Widespread differences were observed in longitudinal change in rCBF between ε4 carriers and non-carriers. The predominant pattern was greater rCBF decline in ε4 carriers. These differences were observed in the frontal, parietal and temporal cortices. The brain regions affected are those that are especially vulnerable to AD pathology. Both ε4 carriers and non-carriers remained free of clinical diagnoses of dementia or mild cognitive impairment during the course of the study. Our findings suggest that APOE ε4-mediated risk for AD is associated with widespread decline in rCBF over time that precedes the onset of dementia. Accelerated rates of decline in brain function in APOE ε4 individuals may contribute to their increased risk for AD and lower age-at-onset.
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影响因子：
37.8
作者：
Wilson, PWF;D'Agostino, RB;Kannel, WB
通讯作者：
Kannel, WB
影响因子：
9.9
作者：
Wishart, H. A.;Saykin, A. J.;Rhodes, C. H.
通讯作者：
Rhodes, C. H.
影响因子：
6
作者：
Morishima-Kawashima, M;Oshima, N;Ihara, Y
通讯作者：
Ihara, Y
影响因子：
9.9
作者：
SAUNDERS, AM;STRITTMATTER, WJ;ROSES, AD
通讯作者：
ROSES, AD
影响因子：
4.2
作者：
Mayeux, R;Small, SA;Stern, Y
通讯作者：
Stern, Y