Massachusetts General Hoospital, Harvard Medical School, Boston, MA, USA.
Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellin, Colombia.
Alzheimers Res Ther. 2021 Jan 15;13(1):27. doi: 10.1186/s13195-020-00765-5.
Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.
Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers.
Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.
Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD.
常染色体显性阿尔茨海默病（ADAD）的神经影像学研究能够描述在临床症状出现前几十年内大脑淀粉样蛋白-β（Aβ）和 tau 积累的轨迹。使用正电子发射断层扫描（PET）测量的区域 tau 积累的纵向速率及其与其他生物标志物和认知变化的关系仍需在 ADAD 中充分描述。
14 名 ADAD 突变携带者（早老素-1 E280A）和 15 名年龄匹配的非携带者来自哥伦比亚家族，在 2-4 年的随访期间接受了 2-3 次 Aβ（11C-匹兹堡化合物 B）和 tau（18F-氟托西匹）PET、结构磁共振成像和神经心理学评估。比较携带者和非携带者之间影像学和认知变量的年化变化率，并在携带者内部评估基线测量值和变化率之间的关系。
纵向测量结果与 ADAD 相关变化的序列一致，从 Aβ 积累开始（在预期症状出现前 16 年，EYO），随后是内嗅皮层（EC）tau（9 EYO）、新皮质 tau（6 EYO）、海马萎缩（6 EYO）和认知下降（4 EYO）。携带者中新皮质 tau 积累的速度最快的是顶叶新皮质（约 9%/年）。EC tau PET 信号在基线时是随后新皮质 tau 积累和携带者内认知下降的重要预测指标。
我们的结果与横断面研究中 ADAD 生物学变化的序列一致，强调了 EC tau 作为早期生物标志物的重要性，以及 ADAD 中 Aβ 负担与新皮质 tau 积累之间的潜在联系。
