Differential Involvement of the Locus Coeruleus in Early- and Late-Onset Alzheimer's Disease: A Potential Mechanism of Clinical Differences?

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 ( < .005). sEOAD participants with greater LC atrophy displayed significantly worse performance on various baseline measures of attentional functioning ( < .05), despite similar global cognition ( = .25). These findings suggest the LC is an important potential driver of clinical and pathological heterogeneity in sEOAD.