McCullough Austin, Chen Charles D, Gordon Brian A, Joseph-Mathurin Nelly, Jack Clifford R, Koeppe Robert, Hornbeck Russ, Koudelis Deborah, McKay Nicole S, Hobbs Diana A, Flores Shaney, Keefe Sarah J, Aggarwal Neelum T, Allegri Ricardo F, Berman Sarah B, Bird Thomas, Black Sandra E, Brooks William S, Chhatwal Jasmeer P, Day Gregory S, Farlow Martin R, Fox Nick C, Gauthier Serge, Honig Lawrence S, Hsiung Ging-Yuek, Jucker Mathias, Levin Johannes, Masellis Mario, Masters Colin, Mendez Patricio Chrem, Ringman John M, Snider B Joy, Salloway Stephen, Schofield Peter R, Shimada Hiroyuki, Suzuki Kazushi, van Dyck Christopher H, Klein Gregory, Clifford David B, Cruchaga Carlos, Hassenstab Jason, Li Yan, McDade Eric, Mills Susan, Morris John C, Perrin Richard J, Supnet-Bell Charlene, Wang Guoqiao, Xiong Chengjie, Bateman Randall J, Benzinger Tammie L S
Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
Mayo Clinic, Rochester, Minnesota, USA.
Alzheimers Dement. 2025 Jul;21(7):e70347. doi: 10.1002/alz.70347.
Monoclonal anti-amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD).
In the DIAN-TU-001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [C]-Pittsburgh compound-B (PiB) positron emission tomography (PET), [F]-fluoro-2-deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI).
Gantenerumab significantly reduced PiB-PET uptake overall and in most regions and showed no changes in FDG-PET or MRI measures. Drug effects were associated with baseline PiB-PET uptake, and the largest effects occurred in medial regions.
Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB-PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design.
Gantenerumab unevenly decreased Aβ burden as measured by PiB-PET across brain regions. The strongest decrease in PiB-PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG-PET metabolism or MRI volumetrics after 4 years.
单克隆抗淀粉样蛋白疗法现已可用，但这些治疗如何影响大脑内部变化仍不清楚。我们研究了显性遗传性阿尔茨海默病（DIAD）试验参与者中淀粉样蛋白清除、葡萄糖代谢和萎缩的整体及区域变化。
在DIAN-TU-001试验中，92名携带者接受了甘特单抗或安慰剂治疗，并接受了一系列神经影像学评估，包括[C] -匹兹堡化合物-B（PiB）正电子发射断层扫描（PET）、[F] -氟代脱氧葡萄糖（FDG）PET和磁共振成像（MRI）。
甘特单抗总体上和在大多数区域显著降低了PiB-PET摄取，并且在FDG-PET或MRI测量中未显示出变化。药物效应与基线PiB-PET摄取相关，最大效应出现在内侧区域。
接受治疗的DIAD参与者，尤其是那些淀粉样蛋白负担较高的参与者，PiB-PET摄取减少，在基底神经节和内侧额叶结构中更为明显。这些结果可能为患者反应和未来药物试验设计提供信息。
通过PiB-PET测量，甘特单抗在不同脑区不均匀地降低了Aβ负担。PiB-PET摄取下降最明显的是基底神经节和内侧额叶结构。对Aβ的药物效应可变部分归因于治疗前存在的负担量。4年后对FDG-PET代谢或MRI体积测量没有区域影响。
