Locus coeruleus alterations in dementia with Lewy bodies: A systematic review.

INTRODUCTION

The locus coeruleus (LC) is a small nucleus located deep within the brainstem, serving as the brain's main source of noradrenergic neurons. Through its extensive projections, it plays a critical role in regulating cognitive processes and arousal. Although LC degeneration has been well documented in Alzheimer's disease and Parkinson's disease, its specific involvement in the pathophysiology of dementia with Lewy bodies (DLB) remains poorly understood.

METHODS

This systematic review, conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, explores the role of LC in the pathogenesis of DLB by synthesizing findings from human neuropathological and neuroimaging research and animal models of α-synucleinopathy.

RESULTS

Although studies directly examining the LC in DLB remain limited, particularly in human living patients, available evidence points to early and severe LC alterations in DLB and suggests that LC dysfunction may contribute to key clinical symptoms such as impaired arousal and anxiety.

DISCUSSION: A better understanding of the mechanisms driving LC dysfunction and neurodegeneration in DLB could facilitate the development of novel biomarkers and, ultimately, symptomatic therapies.

HIGHLIGHTS: Locus coeruleus (LC) alterations are among the earliest changes in dementia with Lewy bodies (DLB).Accumulation of α-synuclein in the LC disrupts noradrenergic function.LC neurodegeneration may contribute to cognitive and neuropsychiatric symptoms.Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) reveals LC signal loss from the prodromal stage of DLB.LC dysfunction emerges as a potential biomarker and therapeutic target in DLB.