Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
Brain. 2017 Sep 1;140(9):2286-2294. doi: 10.1093/brain/awx171.
Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease.
阿尔茨海默病患者可能表现出不同的临床表型。发病年龄大于 65 岁的晚发性阿尔茨海默病患者通常表现为内侧颞叶神经退行性变和以记忆障碍为主的症状，而发病年龄小于 65 岁的早发性阿尔茨海默病患者则表现出更大的皮质受累，其临床表现包括运动障碍、执行功能障碍或视觉空间障碍。我们招募了 20 名早发性阿尔茨海默病患者、21 名晚发性阿尔茨海默病患者、3 名前驱期早发性阿尔茨海默病患者和 13 名前驱期晚发性阿尔茨海默病患者，以及 30 名认知健康的老年对照者，这些患者接受了 18F-AV-1451 tau 正电子发射断层扫描和结构磁共振成像，以探讨早发性和晚发性阿尔茨海默病是否表现出不同的区域 tau 病理学和萎缩模式。在几个皮质区域观察到症状发作年龄较低与 18F-AV-1451 摄取量较高之间存在强烈关联，而在两组患者中，年龄较高与 18F-AV-1451 摄取量均无正相关。将早发性阿尔茨海默病患者与对照组进行比较，结果显示整个皮质的 18F-AV-1451 保留明显更高，而将健康对照组与晚发性阿尔茨海默病患者进行比较，则表现出更高的 18F-AV-1451 保留模式，主要局限于颞叶区域。与对照组相比，早发性阿尔茨海默病组在前额叶和运动前皮质以及下顶叶皮质的摄取量大于晚发性组。这些初步发现表明，年龄可能是阿尔茨海默病异质性的一个重要因素，强调了 tau 正电子发射断层扫描在捕捉阿尔茨海默病患者表型变化方面的潜力。
