Department of Radiology, University of California, San Francisco, USA.
Alzheimers Dement. 2011 Sep;7(5):514-20. doi: 10.1016/j.jalz.2010.12.010.
The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ɛ4 (APOE ɛ4), a genetic risk factor for Alzheimer's disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ɛ4 together on longitudinal volume loss.
We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE ɛ4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ɛ4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer's disease.
An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ɛ4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ɛ4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers.
Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ɛ4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.
大多数与淀粉样蛋白病理学相关的脑容量研究都是横断面研究。载脂蛋白 E4（APOEɛ4）是阿尔茨海默病的遗传风险因素，也与海马体体积减少有关。目前尚无研究考虑淀粉样蛋白病理学和 APOEɛ4 共同对纵向体积损失的影响。
我们评估了脑脊液β-淀粉样蛋白（CSF Aβ）水平异常和 APOEɛ4 携带状态是否与 1 年内海马体体积减少有关。然后，我们评估了 APOEɛ4 状态和 CSF Aβ 是否协同作用，通过回归分析检验交互项的显著性。我们纳入了 297 名参与者：77 名认知正常、144 名轻度认知障碍（MCI）和 76 名阿尔茨海默病患者。
发现异常 CSF Aβ 水平与每组 1 年内海马体体积减少有关。APOEɛ4 仅与认知正常和 MCI 组的海马体体积减少有关。在 MCI 组中，APOEɛ4 携带者 CSF Aβ 异常时，其海马体体积减少的协同作用大于非携带者。
基线 CSF Aβ 可预测海马体体积减少的进展。APOEɛ4 携带状态放大了 MCI 中神经退行性变的程度。了解遗传风险和淀粉样蛋白病理学之间相互作用的影响，对于临床试验和我们对疾病过程的理解非常重要。
