载脂蛋白 E ε4 基因型对阿尔茨海默病中淀粉样蛋白-β 和 tau 积累的影响。
Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer's disease.
机构信息
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 20 Eonjuro 63-gil, Gangnam-gu, Seoul, South Korea.
Biostatistics Collaboration Unit, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
出版信息
Alzheimers Res Ther. 2020 Oct 31;12(1):140. doi: 10.1186/s13195-020-00710-6.
BACKGROUND
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.
METHODS
Among 272 individuals who underwent PET scans (F-florbetaben for Aβ and F-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.
RESULTS
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.
CONCLUSIONS
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.
背景
评估载脂蛋白 E（ApoE）ε4 基因型对阿尔茨海默病（AD）谱中淀粉样蛋白-β（Aβ）和 tau 负担及其纵向变化的影响。
方法
在 272 名接受正电子发射断层扫描（F-氟比洛芬用于 Aβ 和 F-氟他西普用于 tau）和 ApoE 基因分型的患者中，有 187 名完成了 2 年的随访正电子发射断层扫描。在纠正部分容积效应后，我们比较了ε4+和ε4-组之间 Aβ 和 tau 负担的标准化摄取值比（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。
结果
ε4+组在弥漫性皮质区域的基线 Aβ 负担更大，在外侧、内侧颞叶、扣带回和岛叶皮质的 tau 负担更大。在 ApoE ε4+组中，额顶叶、枕叶、外侧和内侧颞叶皮质的 tau 积累率更高。在 Aβ+个体中，内侧颞叶皮质的 tau 基线负担更大，而 Aβ 负担在ε4-组中相反更大。在外侧颞叶皮质的一小部分区域，ε4+组的 tau 积累率更高。即使在调整了皮质 Aβ 总负担后，ApoE ε4 对增强的 tau 积累的影响仍然存在。
结论
在 ε4 携带者中，tau 的进行性积累可能更为突出，尤其是在内侧和外侧颞叶皮质。ApoE ε4 等位基因对 Aβ 负担的影响因现有的淀粉样蛋白沉积而异，并且可能会增强 AD 谱中 tau 进行性积累的易感性，而与 Aβ 无关。
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