Metabolomic Relationships Between Lung Cancer and Alzheimer's Disease Using Serum Nuclear Magnetic Resonance Spectroscopy

ABSTRACT Lung cancer (LC) and Alzheimer's disease (AD) are both age‐associated diseases with high rates of mortality. Studies have reported a possible inverse relationship between LC and AD incidences; however, possible shared molecular mechanisms have not been well investigated. Better characterizations of both diseases and their potential molecular relationships may advance the development of successful therapies for both LC and AD. Metabolomics, as a holistic study of the entire measurable metabolome, has the potential to probe into their metabolic connections. Herein, we used high‐resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to study 36 human serum samples collected from primary lung adenocarcinoma patients with or without AD, or AD and related dementia (ADRD). We identified 88 metabolites with 66 metabolites differentiating LC patients from controls, and 80 metabolites discerning LC patients without ADRD from those with ADRD. Our results demonstrate the capability of metabolomics to reveal inversely dysregulated glycolysis, oxidative phosphorylation, and proline metabolism in LC and ADRD.