Department of Radiology, University of California at San Francisco, 505 Parnassus Avenue M-391, San Francisco, CA 94143, USA.
Neurology. 2010 Nov 30;75(22):1976-81. doi: 10.1212/WNL.0b013e3181ffe4d1. Epub 2010 Oct 27.
To determine whether elderly normal APOE E2 (APOE2) carriers exhibit slower rates of hippocampal atrophy and memory decline compared to APOE3/3 carriers. We also determined whether APOE2 carriers have less Alzheimer pathology as reflected by CSF biomarkers.
We included longitudinal data from 134 cognitively normal individuals (27 APOE2/2 or E2/3, 107 APOE3/3) from the Alzheimer's Disease Neuroimaging Initiative, a prospective cohort study. A linear mixed-effects model was used to determine how APOE2 affected rates of hippocampal atrophy and cognitive change over time. In a subsample of 72 individuals who also underwent CSF analysis, an ordinary least-squares regression was used to determine whether CSF β-amyloid (Aβ), total tau, and phosphorylated tau-181 (p-tau) differed by APOE2 status.
APOE2 carriers demonstrated slower rates of hippocampal atrophy (p = 0.004). The mean rate of hippocampal atrophy among APOE2 carriers was -33 mm(3)/year (95% confidence interval -65 to +0.4), or -0.5%/year, compared to -86 mm(3)/year (95% confidence interval -102 to -71), or -1.3%/year, in the APOE3/3 group. No differences in the rates of episodic memory (p = 0.23) or overall cognitive change (p = 0.90) were detected. In the CSF subsample, APOE2 carriers had higher levels of CSF Aβ (p = 0.01), lower p-tau (p = 0.02), and marginally lower tau (p = 0.12).
A slower rate of hippocampal atrophy in normal APOE2 carriers is consistent with the lower risk of Alzheimer disease in these individuals. We hypothesize that the slower atrophy rate is related to decreased preclinical Alzheimer pathology.
确定与 APOE3/3 携带者相比，老年正常 APOE E2（APOE2）携带者的海马体萎缩和记忆衰退速度是否较慢。我们还确定 APOE2 携带者的脑脊液生物标志物是否反映出较少的阿尔茨海默病病理。
我们纳入了来自阿尔茨海默病神经影像学倡议（一项前瞻性队列研究）的 134 名认知正常个体（27 名 APOE2/2 或 E2/3，107 名 APOE3/3）的纵向数据。使用线性混合效应模型来确定 APOE2 如何影响随时间推移的海马体萎缩和认知变化的速度。在也接受脑脊液分析的 72 名个体的亚样本中，使用普通最小二乘回归来确定 CSFβ-淀粉样蛋白（Aβ）、总 tau 和磷酸化 tau-181（p-tau）是否因 APOE2 状态而异。
APOE2 携带者表现出较慢的海马体萎缩速度（p = 0.004）。APOE2 携带者的平均海马体萎缩速度为-33mm³/年（95%置信区间-65 至+0.4），或-0.5%/年，而 APOE3/3 组的平均速度为-86mm³/年（95%置信区间-102 至-71），或-1.3%/年。未检测到情节记忆（p = 0.23）或整体认知变化（p = 0.90）的速度差异。在脑脊液亚样本中，APOE2 携带者的 CSF Aβ 水平更高（p = 0.01），p-tau 水平更低（p = 0.02），tau 水平略低（p = 0.12）。
正常 APOE2 携带者的海马体萎缩速度较慢，这与这些个体患阿尔茨海默病的风险较低一致。我们假设较慢的萎缩速度与临床前阿尔茨海默病病理减少有关。
