Julien Lagarde MD, PhD, Piyush Maiti MS, Daniel R. Schonhaut PhD, Ganna Blazhenets PhD, Jiaxiuxiu Zhang MS, Ani Eloyan PhD, Maryanne Thangarajah MS, Alexander Taurone MS, Isabel Elaine Allen PhD, David N. Soleimani-Meigooni MD, Ehud Zeltzer MD, Charles Windon MD, Maison Abu Raya MD, Agathe Vrillon MD, PhD, Karen Smith BS, Ranjani Shankar BS, Alinda Amuiri BS, Salma Rocha BA, Dustin B. Hammers PhD, Jeffrey L. Dage PhD, Kelly N. Nudelman PhD, Kala Kirby BS, Paul Aisen MD, Robert Koeppe PhD, Susan M. Landau PhD, Maria C. Carrillo PhD, Alexandra Touroutoglou PhD, Michael Brickhouse BS, Prashanthi Vemuri PhD, Laurel Beckett PhD, Rema Raman PhD, Alireza Atri MD, PhD, Gregory S. Day MD, Ranjan Duara MD, Neill R. Graff-Radford MD, Lawrence S. Honig MD, PhD, David T. Jones MD, Joseph C. Masdeu MD, PhD, Mario F. Mendez MD, PhD, Kyle Womack MD, Erik Musiek MD, PhD, Chiadi U. Onyike MD, Meghan Riddle MD, Ian M. Grant MD, Emily Rogalski PhD, Erik C. B. Johnson MD, PhD, Stephen Salloway MD, Sharon Sha MD, R. Scott Turner MD, PhD, Thomas S. Wingo MD, David A. Wolk MD, Bradford C. Dickerson MD, Liana G. Apostolova MD, Renaud La Joie PhD, Gil D. Rabinovici MD, the LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative
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Grant MD, Emily Rogalski PhD, Erik C. B. Johnson MD, PhD, Stephen Salloway MD, Sharon Sha MD, R. Scott Turner MD, PhD, Thomas S. Wingo MD, David A. Wolk MD, Bradford C. Dickerson MD, Liana G. Apostolova MD, Renaud La Joie PhD, Gil D. Rabinovici MD, the LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/ana.27233","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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, <i>APOE</i> genotype, and cognition.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74–82) than in ADNI (71%, 95% CI = 67–75, <i>p</i> = 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, <i>p</i> < 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 <i>lower</i> 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.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>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. 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引用次数: 0
摘要
目的：早发性阿尔茨海默病（EOAD）和晚发性阿尔茨海默病（LOAD）在许多方面存在差异。在这里，我们解决了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可能存在差异的问题，由于缺乏大规模的比较研究，这一问题仍未得到解决。方法：来自多中心纵向早发性阿尔茨海默病研究（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。我们比较了两个队列的淀粉样蛋白PET结果（基于视觉读取和量化示踪剂摄取的阳性率，以Centiloids [CLs]表示），并研究了它们与年龄、性别、APOE基因型和认知的关系。结果：lead患者淀粉样蛋白阳性率（78%，95%可信区间[CI] = 74 ~ 82）高于ADNI患者（71%,95% CI = 67 ~ 75, p = 0.02）。较低的最小精神状态检查（MMSE）和APOE4基因型增加了两个队列中淀粉样蛋白阳性的几率。视觉阳性扫描显示，LEADS （EOAD，平均= 95.3±26.1）的CLs高于ADNI （LOAD，平均= 80.9±36.8,p）。解释：淀粉样蛋白病理负担的差异可能导致散发性EOAD和LOAD的临床和解剖模式的差异，并对优化每组的治疗策略具有重要意义。Ann neurol 2025。
Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts
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
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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