The interplay of homeostasis, inflammation, and oxidative stress in neurodegenerative disorders: the role of biological markers, antioxidants, lithium, and TMS - a proposed framework for preventing neurodegenerative disorders through biomarkers and multimodal therapies.

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most significant health challenges of aging, characterized by progressive cognitive and motor decline. Increasing evidence suggests that these conditions are not inevitable outcomes of aging but may instead be driven by preventable mechanisms involving oxidative stress, chronic inflammation, and disruptions in homeostasis. This manuscript proposes a preventive framework that integrates validated biomarkers: glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and YKL-40 or CHI3L1 by its more commonly used name: Chitinase-3-like protein 1 with multimodal therapeutic interventions, including antioxidants, lithium, and transcranial magnetic stimulation (TMS). Oxidative stress is positioned as a central mediator of neurodegeneration, with biomarkers serving as early indicators that enable detection before irreversible neuronal loss. This supports our proposal that NfL is not only a marker of pathology but also a measurable indicator of lithium's effect in stabilizing axons and reducing neurodegeneration. These results align with our framework, which places TMS as a synergistic tool with lithium and antioxidants to modify both oxidative and neuroplastic pathways with a translational preventive strategy. Importantly, recent findings published in demonstrated that reducing dietary lithium by more than 50% in AD mouse models accelerated amyloid-