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

Early-onset Alzheimer's disease (EOAD) has been associated with an increased likelihood of atypical clinical manifestations such as attentional impairment, yet the cause of this heterogeneity remains unclear. The locus coeruleus (LC) is implicated early in Alzheimer's disease pathology and is associated with attentional functioning. This study investigated post-mortem atrophy of the LC in EOAD and late-onset Alzheimer's disease (LOAD) in a large, well-characterized sample. Results show nearly four times greater likelihood of higher LC atrophy in EOAD as compared to LOAD after controlling for other measures of pathological progression ( p < .005). Follow-up analyses within the EOAD group revealed that compared to those who displayed mild or no LC atrophy at autopsy, those with moderate-severe atrophy of the LC displayed significantly worse performance on various baseline measures of attentional functioning ( p < .05), despite similar overall cognition ( p = .25). These findings suggest the LC is an important potential driver of clinical and pathological heterogeneity in EOAD.