Sporadic early-onset Alzheimer’s disease (sEOAD) is often associated with atypical clinical features, yet the cause of this heterogeneity remains unclear. This study investigated post-mortem atrophy of the locus coeruleus (LC) in sEOAD and late-onset Alzheimer’s disease (LOAD). Levels of LC atrophy, as estimated by pathologist-rating of hypopigmentation, were compared between sEOAD (n = 115) and LOAD (n = 672) participants while controlling for other measures of pathological progression. Subsequent analyses compared low vs. high LC atrophy sEOAD subgroups on neuropsychological test performance. Results show nearly 4 times greater likelihood of higher LC atrophy in sEOAD as compared to LOAD (p < .005). sEOAD participants with greater LC atrophy displayed significantly worse performance on various baseline measures of attentional functioning (p < .05), despite similar global cognition (p = .25). These findings suggest the LC is an important potential driver of clinical and pathological heterogeneity in sEOAD.

散发性早发性阿尔茨海默病 (sEOAD) 通常与非典型临床特征相关，但这种异质性的原因仍不清楚。本研究调查了死后 sEOAD 和迟发性阿尔茨海默病 (LOAD) 中蓝斑 (LC) 的萎缩。根据病理学家对色素沉着减退的评级估计的 LC 萎缩水平在 sEOAD (n = 115) 和 LOAD (n = 672) 参与者之间进行了比较，同时控制了其他病理进展指标。随后的分析比较了低和高 LC 萎缩 sEOAD 亚组对神经心理学测试性能的影响。结果显示，与 LOAD 相比，sEOAD 中出现更高 LC 萎缩的可能性高近 4 倍（p<.005）。尽管整体认知相似 ( p = .25)，但LC 萎缩程度更大的 sEOAD 参与者在注意力功能的各种基线测量中表现出明显更差的表现( p < .05)。这些发现表明 LC 是 sEOAD 临床和病理异质性的重要潜在驱动因素。