Xiong Chengjie, Roe Catherine M, Buckles Virginia, Fagan Anne, Holtzman David, Balota David, Duchek Janet, Storandt Martha, Mintun Mark, Grant Elizabeth, Snyder Abraham Z, Head Denise, Benzinger Tammie L S, Mettenburg Joseph, Csernansky John, Morris John C
Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA.
Arch Neurol. 2011 Oct;68(10):1313-9. doi: 10.1001/archneurol.2011.208.
To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities.
Adult Children Study.
Washington University's Charles F. and Joanne Knight Alzheimer's Disease Research Center.
A total of 269 cognitively normal middle- to older-aged individuals with and without an FH for AD.
Clinical and cognitive measures, magnetic resonance imaging-based brain volumes, diffusion tensor imaging-based white matter microstructure, cerebrospinal fluid biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography using the [(11)C] benzothiazole tracer, Pittsburgh compound B.
A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid Aβ42; the ε4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid Aβ42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive FH compared with the decrease for those without. The variation of cerebrospinal fluid tau and Pittsburgh compound B mean cortical binding potential increased by age. For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential. A positive FH was associated with decreased fractional anisotropy from diffusion tensor imaging in the genu and splenium of the corpus callosum.
Independent of APOE4, FH is associated with age-related change of several cerebrospinal fluid, Pittsburgh compound B, and diffusion tensor imaging biomarkers in cognitively normal middle- to older-aged individuals, suggesting that non- APOE susceptibility genes for AD influence AD biomarkers.
评估仅阿尔茨海默病（AD）家族史是否会影响AD生物标志物异常。
成年子女研究。
华盛顿大学查尔斯·F·和乔安妮·奈特阿尔茨海默病研究中心。
共269名认知正常的中老年人，有或无AD家族史。
临床和认知指标、基于磁共振成像的脑容量、基于扩散张量成像的白质微结构、脑脊液生物标志物，以及使用[（11）C]苯并噻唑示踪剂匹兹堡化合物B通过正电子发射断层扫描对脑纤维状淀粉样蛋白进行分子成像。
AD家族史阳性与脑脊液Aβ42随年龄下降有关；载脂蛋白E（APOE4）的ε4等位基因未改变这种效应。与无APOE4的个体相比，有APOE4的个体经年龄调整后的脑脊液Aβ42降低，且家族史阳性个体的降低幅度大于无家族史个体。脑脊液tau和匹兹堡化合物B平均皮质结合潜能的变化随年龄增加。对于年龄小于55岁的个体，平均皮质结合潜能随年龄增加与APOE4有关，而与家族史无关。对于年龄大于55岁的个体，家族史阳性和APOE4阳性意味着平均皮质结合潜能随年龄增加最快。家族史阳性与胼胝体膝部和压部扩散张量成像的各向异性分数降低有关。
独立于APOE4，家族史与认知正常的中老年人中几种脑脊液、匹兹堡化合物B和扩散张量成像生物标志物的年龄相关变化有关，提示AD的非APOE易感基因影响AD生物标志物。
