Resnick Susan M, Bilgel Murat, Moghekar Abhay, An Yang, Cai Qing, Wang Mei-Cheng, Thambisetty Madhav, Prince Jerry L, Zhou Yun, Soldan Anja, Wong Dean F, O'Brien Richard J, Ferrucci Luigi, Albert Marilyn S
Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Neurobiol Aging. 2015 Aug;36(8):2333-9. doi: 10.1016/j.neurobiolaging.2015.04.001. Epub 2015 Apr 4.
Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and (11)C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ1-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease.
载脂蛋白E(APOE)基因型影响阿尔茨海默病的发病年龄,但对疾病进展的影响尚不清楚。我们在两个不同的纵向队列中使用两种不同的β淀粉样蛋白(Aβ)测量方法,研究了Aβ水平及其与APOE基因型的关系变化。在113名巴尔的摩纵向衰老研究参与者(平均年龄77.3岁;107名正常,6名认知受损)中,使用正电子发射断层扫描(PET)成像和(11)C-匹兹堡化合物-B(PiB)测量Aβ积累;在207名BIOCARD研究参与者(平均年龄62岁;195名正常,12名认知受损)中,检测脑脊液(CSF)Aβ1-42。两个队列的参与者均进行了多达7次的系列评估(平均2.3 - 2.4次)。PET-PiB滞留量纵向增加,CSF Aβ1-42纵向下降。独立于年龄和性别,APOE ε4与较高的PET-PiB滞留量和较低的CSF Aβ1-42显著相关,但APOE基因型并未显著影响Aβ随时间的变化。APOE ε4携带者在疾病进程中可能进展得更远,这与早期脑Aβ沉积一致,并为APOE基因型对阿尔茨海默病发病年龄的影响提供了生物学基础。