Age-dependent brain pigmentation drives early neuroinflammatory molecular signatures linked to neurodegeneration

The study focuses on neuromelanin, a pigment that accumulates with age in catecholaminergic neurons of the substantia nigra, ventral tegmental area, and locus coeruleus—regions selectively vulnerable to degeneration in Parkinson's disease (PD). Elevated neuromelanin levels have been previously associated with PD-like phenotypes, but the underlying molecular pathways were unclear. This preprint identifies specific neuroinflammatory molecular signatures driven by neuromelanin, suggesting a causal role in early disease processes. These findings could help explain the selective vulnerability of dopaminergic neurons and point toward new therapeutic targets for neuroprotection.