Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer's disease.
Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer's disease.
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DOI：
10.1186/s13195-020-00710-6
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发表时间：
2020-10-31
期刊：
影响因子：
--
通讯作者：
Lyoo CH
中科院分区：
文献类型：
--
作者：
Baek MS;Cho H;Lee HS;Lee JH;Ryu YH;Lyoo CH
评估载脂蛋白 E (ApoE) ε4 基因型对淀粉样蛋白-β (Aβ) 和 tau 蛋白负荷的影响及其在阿尔茨海默病 (AD) 谱中的纵向变化。在 272 名接受 PET 扫描（18F-florbetaben 用于 Aβ 扫描，18F-flortaucipir 用于 tau）和 ApoE 基因分型的个体中，187 名个体完成了 2 年随访 PET 扫描。校正部分体积效应后，我们比较了 ε4+ 和 ε4− 组之间 Aβ 和 tau 负荷的标准化摄取值比 (SUVR)。通过使用线性混合效应模型，我们测量了 ApoE ε4+ 和 ε4− 组中 SUVR 的变化。 ε4+组在弥漫性皮质区域显示出更大的基线Aβ负荷，在外侧、内侧颞叶、扣带皮层和岛叶皮质中显示出更大的tau负荷。 ε4+组的顶叶、枕叶、外侧和内侧颞叶皮质中的Tau蛋白积累率较高。在 Aβ+ 个体中，内侧颞叶皮层的基线 tau 负荷更大，而 ε4− 组的 Aβ 负荷相反更大。 ε4+ 组在外侧颞叶皮层的一个小区域中 Tau 积累率较高。即使在调整了整体皮质 Aβ 负担后，ApoE ε4 对增强 tau 积累的作用仍然持续存在。进行性 tau 蛋白积累在 ε4 携带者中可能更为突出，特别是在内侧和外侧颞叶皮质中。 ApoE ε4 等位基因对 Aβ 负荷具有不同的影响，具体取决于现有的淀粉样变性，并且可能会增强 AD 谱中不依赖于 Aβ 的渐进 tau 积累的脆弱性。本文随附的补充信息为 10.1186/s13195-020-00710-6。
To assess the effects of apolipoprotein E (ApoE) ε4 genotype on amyloid-β (Aβ) and tau burden and their longitudinal changes in Alzheimer’s disease (AD) spectrum. Among 272 individuals who underwent PET scans (18F-florbetaben for Aβ and 18F-flortaucipir for tau) and ApoE genotyping, 187 individuals completed 2-year follow-up PET scans. After correcting for the partial volume effect, we compared the standardized uptake value ratio (SUVR) for Aβ and tau burden between the ε4+ and ε4− groups. By using a linear mixed-effect model, we measured changes in SUVR in the ApoE ε4+ and ε4− groups. The ε4+ group showed greater baseline Aβ burden in the diffuse cortical regions and greater tau burden in the lateral, and medial temporal, cingulate, and insula cortices. Tau accumulation rate was higher in the parietal, occipital, lateral, and medial temporal cortices in the ε4+ group. In Aβ+ individuals, baseline tau burden was greater in the medial temporal cortex, while Aβ burden was conversely greater in the ε4− group. Tau accumulation rate was higher in the ε4+ group in a small region in the lateral temporal cortex. The effect of ApoE ε4 on enhanced tau accumulation persisted even after adjusting for the global cortical Aβ burden. Progressive tau accumulation may be more prominent in ε4 carriers, particularly in the medial and lateral temporal cortices. ApoE ε4 allele has differential effects on the Aβ burden depending on the existing amyloidosis and may enhance vulnerability to progressive tau accumulation in the AD spectrum independent of Aβ. Supplementary information accompanies this paper at 10.1186/s13195-020-00710-6.
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影响因子：
2.9
作者：
Garai, Kanchan;Verghese, Philip B.;Baban, Berevan;Holtzman, David M.;Frieden, Carl
通讯作者：
Frieden, Carl
DOI：
10.1016/j.jalz.2017.04.011
发表时间：
2017-12
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Crane PK;Trittschuh E;Mukherjee S;Saykin AJ;Sanders RE;Larson EB;McCurry SM;McCormick W;Bowen JD;Grabowski T;Moore M;Bauman J;Gross AL;Keene CD;Bird TD;Gibbons LE;Mez J;Executive Prominent Alzheimer's Disease: Genetics and Risk Factors (EPAD:GRF) Investigators
通讯作者：
Executive Prominent Alzheimer's Disease: Genetics and Risk Factors (EPAD:GRF) Investigators
影响因子：
25.8
作者：
Lautner, Ronald;Palmqvist, Sebastian;Hansson, Oskar
通讯作者：
Hansson, Oskar
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
9.9
作者：
Lim, Yen Ying;Mormino, Elizabeth C.
通讯作者：
Mormino, Elizabeth C.