Whitwell Jennifer L, Tosakulwong Nirubol, Weigand Stephen D, Graff-Radford Jonathan, Duffy Joseph R, Clark Heather M, Machulda Mary M, Botha Hugo, Utianski Rene L, Schwarz Christopher G, Senjem Matthew L, Strand Edythe A, Ertekin-Taner Nilufer, Jack Clifford R, Lowe Val J, Josephs Keith A
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
J Alzheimers Dis. 2020;74(1):377-389. doi: 10.3233/JAD-190699.
Rates of amyloid-β (Aβ) accumulation have been characterized across the cognitively normal to typical Alzheimer's dementia spectrum, but little is known about Aβ accumulation in atypical Alzheimer's disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD).
We aimed tocharacterize longitudinal Aβ accumulation anddetermine the influence of age, apolipoprotein E (APOE) genotype, disease duration, and sexin atypical AD and FTLD.
322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serialPiB-PET scans (42 atypical AD, 31 FTLD). Global Aβ standard uptake value ratios were calculated for every scan. Mixed effects models were used to assess the effect of age, APOE genotype, disease duration, and sex on baseline and change measures of Aβ.
Atypical AD showed higher baseline Aβ than FTLD. Rate of Aβ accumulation was not associated with baseline Aβ in either group. Older age was associated with greater baseline Aβ and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOEɛ4 genotype was associated with greater baseline Aβ in FTLD but did not influence rates of accumulation. Rates of Aβ accumulation were faster in FTLD patents with time from onset-to-PET≤4 years. Female sex was associated with faster rates of accumulation in atypical AD.
Accumulation of Aβ is observed in atypical AD and FTLD, although different demographic factors influence accumulation in these diseases providing insight into potentially different biological mechanisms of Aβ deposition.
淀粉样β蛋白（Aβ）的积累速率已在认知正常到典型阿尔茨海默病痴呆症的范围内得到了表征，但对于非典型阿尔茨海默病（AD）和其他神经退行性疾病，如额颞叶变性（FTLD）中的Aβ积累情况知之甚少。
我们旨在表征Aβ的纵向积累情况，并确定年龄、载脂蛋白E（APOE）基因型、疾病持续时间和性别对非典型AD和FTLD的影响。
322名患者（138例非典型AD，184例FTLD）接受了匹兹堡化合物B正电子发射断层扫描（PET），其中73例进行了连续的PiB-PET扫描（42例非典型AD，31例FTLD）。对每次扫描计算全脑Aβ标准摄取值比率。使用混合效应模型评估年龄、APOE基因型、疾病持续时间和性别对Aβ基线和变化指标的影响。
非典型AD的基线Aβ水平高于FTLD。两组中Aβ的积累速率均与基线Aβ无关。在FTLD中，年龄较大与更高的基线Aβ水平和更快的积累速率相关。在70岁以下的患者中，非典型AD的积累速率比FTLD更快。APOEɛ4基因型与FTLD中更高的基线Aβ水平相关，但不影响积累速率。从发病到PET检查时间≤4年的FTLD患者中，Aβ积累速率更快。在非典型AD中，女性的积累速率更快。
在非典型AD和FTLD中均观察到Aβ的积累，尽管不同的人口统计学因素影响这些疾病中的Aβ积累，这为深入了解Aβ沉积潜在的不同生物学机制提供了线索。
