From the New York University School of Medicine (L.M., J.M., W.H.T., Y.L., N.S., A.G., S.W., R.O., P.M., L.G., M.J.d.L.); and Weill Cornell Medical College (S.V.), New York.
Neurology. 2014 Mar 4;82(9):752-60. doi: 10.1212/WNL.0000000000000181. Epub 2014 Feb 12.
This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD.
Fifty-two NL individuals received MRI, (11)C-Pittsburgh compound B (PiB)-PET, and (18)F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n = 13/group, aged 32-72 years, 60% female, 30% APOE ε4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH-). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volume-corrected PiB retention, and FDG metabolism across FH groups and vs FH-.
NL FHmp showed more severe abnormalities in all 3 biomarkers vs the other groups regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in FHmp, intermediate in FHm, and lowest in FHp and FH-. GMV reductions were highest in FHmp and intermediate in FHm and FHp vs FH-. In all FH+ groups, amyloid-β deposition exceeded GMV loss and hypometabolism exceeded GMV loss (p < 0.001), while amyloid-β deposition exceeded hypometabolism in FHmp and FHp but not in FHm.
These biomarker findings show a "LOAD parent-dose effect" in NL individuals several years, if not decades, before possible clinical symptoms.
本脑成像研究旨在探讨认知正常（NL）个体中，有 2 位受晚发性阿尔茨海默病（LOAD）影响的父母者与仅有 1 位受 LOAD 影响的父母者相比，是否具有更广泛的阿尔茨海默病病理学证据。
52 名 NL 个体接受了 MRI、（11）C-匹兹堡化合物 B（PiB）-正电子发射断层扫描（PET）和（18）F-氟-2-脱氧葡萄糖（FDG）-PET 检查。这些 NL 个体分为 4 个在人口统计学上平衡的组（每组 13 人，年龄 32-72 岁，60%为女性，30%为 APOE ε4 携带者），包括有母系（FHm）、父系（FHp）和母系及父系（FHmp）LOAD 家族史的 NL 个体，以及无家族史（FH-）的 NL 个体。统计参数映射、体素形态计量学和 z 分数映射用于比较 FH 组与 FH-组之间的 MRI 灰质体积（GMVs）、部分容积校正的 PiB 保留率和 FDG 代谢。
NL FHmp 组在所有 3 种生物标志物方面均比其他组出现更严重的异常，表现为受累区域的数量和损害程度。PiB 保留和低代谢在 FHmp 中最为明显，在 FHm 中次之，在 FHp 和 FH-中最低。GMV 减少在 FHmp 中最高，在 FHm 和 FHp 中次之，在 FH-中最低。在所有 FH+组中，淀粉样蛋白-β沉积超过 GMV 损失，低代谢超过 GMV 损失（p<0.001），而在 FHmp 和 FHp 中淀粉样蛋白-β沉积超过低代谢，但在 FHm 中并非如此。
这些生物标志物发现表明，在可能出现临床症状的几年甚至几十年前，NL 个体中存在“LOAD 父母剂量效应”。
