Impact of Alzheimer's disease risk factors and local neuromelanin content on the transcriptomic landscape of the human locus coeruleus.

ABSTRACT: The locus coeruleus (LC) is a small noradrenergic nucleus in the dorsal pons that sends projections across the brain regulating sleep, arousal, attention, stress responses, and some forms of cognition. LC neurons show pathology in the earliest stages of Alzheimer's disease (AD), including age-related accumulation of hyperphosphorylated tau (pTau) and accelerated loss of neuromelanin (NM) pigmentation. NM-sensitive neuroimaging of the LC predicts previous cognitive decline, clinical severity, and future AD progression. While these findings suggest that the LC plays an etiologic role in AD, the molecular landscape of the LC prior to clinical manifestation of sporadic AD remains largely uncharacterized. This information is critical for developing interventions that preserve LC integrity and f

SUBMITTER: Mulvey B 

PROVIDER: S-EPMC12636595 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature