散发性早发型与晚发型阿尔茨海默病中的淀粉样蛋白PET：LEADS和ADNI队列的比较
Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.
作者信息
Lagarde Julien, Maiti Piyush, Schonhaut Daniel R, Blazhenets Ganna, Zhang Jiaxiuxiu, Eloyan Ani, Thangarajah Maryanne, Taurone Alexander, Allen Isabel Elaine, Soleimani-Meigooni David N, Zeltzer Ehud, Windon Charles, Abu Raya Maison, Vrillon Agathe, Smith Karen, Shankar Ranjani, Amuiri Alinda, Rocha Salma, Hammers Dustin B, Dage Jeffrey L, Nudelman Kelly N, Kirby Kala, Aisen Paul, Koeppe Robert, Landau Susan M, Carrillo Maria C, Touroutoglou Alexandra, Brickhouse Michael, Vemuri Prashanthi, Beckett Laurel, Raman Rema, Atri Alireza, Day Gregory S, Duara Ranjan, Graff-Radford Neill R, Honig Lawrence S, Jones David T, Masdeu Joseph C, Mendez Mario F, Womack Kyle, Musiek Erik, Onyike Chiadi U, Riddle Meghan, Grant Ian M, Rogalski Emily, Johnson Erik C B, Salloway Stephen, Sha Sharon, Turner R Scott, Wingo Thomas S, Wolk David A, Dickerson Bradford C, Apostolova Liana G, La Joie Renaud, Rabinovici Gil D
机构信息
Department of Neurology, University of California, San Francisco, San Francisco, CA.
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI.
出版信息
Ann Neurol. 2025 Aug;98(2):236-248. doi: 10.1002/ana.27233. Epub 2025 Mar 17.
OBJECTIVE
Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large-scale comparative studies.
METHODS
Three hundred ninety-nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition.
RESULTS
The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74-82) than in ADNI (71%, 95% CI = 67-75, p = 0.02). Lower Mini-Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid-positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD.
INTERPRETATION
Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236-248.
目的
早发型阿尔茨海默病（EOAD）和晚发型阿尔茨海默病（LOAD）在许多方面存在差异。在此，我们探讨通过正电子发射断层扫描（PET）测量的纤维状淀粉样蛋白病理学可能存在的差异问题，由于缺乏大规模的比较研究，该问题仍未得到解决。
方法
来自多中心纵向早发型阿尔茨海默病研究（LEADS）的399名年龄小于65岁的认知障碍参与者和来自阿尔茨海默病神经影像学倡议（ADNI）的450名年龄大于65岁的认知障碍参与者接受了临床评估、脑磁共振成像（MRI）和淀粉样蛋白PET检查，并被纳入本研究。我们比较了两个队列之间的淀粉样蛋白PET结果（基于视觉判读的阳性率和以百分离度[CLs]表示的定量示踪剂摄取），并研究了它们与年龄、性别、APOE基因型和认知的关联。
结果
LEADS队列中的淀粉样蛋白阳性率（78%，95%置信区间[CI]=74-82）高于ADNI队列（71%，95%CI=67-75，p=0.02）。较低的简易精神状态检查表（MMSE）评分和APOE4基因型增加了两个队列中淀粉样蛋白阳性的几率。在LEADS队列中，视觉上呈阳性的扫描的CLs（EOAD，平均值=95.3±26.1）高于ADNI队列（LOAD，平均值=80.9±36.8，p<0.0001），主要在顶叶皮质/楔前叶、颞上叶和额叶皮质。在淀粉样蛋白阳性患者中，（1）两个队列中女性患者的CLs更高；（2）在EOAD中，APOE4携带者与较低的CLs相关，而在LOAD中未观察到这种情况；（3）EOAD中CLs与MMSE评分之间的相关性明显强于LOAD。
解读
淀粉样蛋白病理学负担的差异可能导致散发性EOAD和LOAD在临床和解剖模式上的差异，并对优化每组的治疗策略具有启示意义。《神经病学纪事》2025年；98：236-248。
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