Serum optineurin (a mitophagy receptor) was measured in 458 older adults (controls, MCI, AD, and mixed AD/vascular dementia), and Aβ1-42-induced mitophagy dynamics were studied in SH-SY5Y neuroblastoma cells over time.
Serum optineurin was significantly lower in MCI, AD, and mixed AD/vascular dementia groups vs. controls (p < 0.001 for all); serum 4-HNE (oxidative stress marker) was elevated in MCI and AD. In vitro, Aβ1-42 caused an early rise in mitophagy and optineurin expression, followed by a later decline alongside impaired mitochondrial quality-control, apoptosis, and reduced cell viability.
The cross-sectional serum cohort cannot establish causality or temporal sequence of optineurin changes; the in vitro model uses a neuroblastoma cell line (SH-SY5Y), which may not fully replicate neuronal biology in vivo; peripheral serum optineurin levels may not directly reflect central nervous system mitophagy status.
Serum optineurin shows promise as a peripheral biomarker for MCI and AD, but further longitudinal and mechanistic validation is needed before clinical use. Clinicians should note that mitophagy impairment may be detectable systemically, potentially opening a window for earlier disease monitoring.
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