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

Leonard Lado, MD, ABPN, RPh^1*Aruna Misir, Medical Student and Researcher^1,2

• ¹Lado Healing Institute, Bonita Springs, United States
• ²Xavier University School of Medicine, Oranjestad, Netherlands

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) represent major challenges of aging, marked by progressive cognitive and motor decline. Increasing evidence suggests these conditions are not inevitable consequences of aging but may arise from preventable mechanisms involving oxidative stress, chronic inflammation, and disruptions in homeostasis. This manuscript proposes a preventive framework integrating validated biomarkers—glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and YKL-40 or chitinase-3-like protein 1 (CHI3L1)—with multimodal therapeutic interventions including antioxidants, lithium, and transcranial magnetic stimulation (TMS). Oxidative stress is positioned as a central mediator of neurodegeneration, while biomarkers serve as early indicators that enable detection before irreversible neuronal loss. For example, NfL is proposed not only as a marker of pathology but also as a measurable indicator of lithium’s effect in stabilizing axons and reducing neurodegeneration. Recent findings published in Nature (Aron et al., 2025) demonstrated that reducing dietary lithium by more than 50% in AD mouse models accelerated amyloid-β and tau pathology, increased microglial activation, and caused cognitive decline. Remarkably, lithium supplementation prevented these changes and preserved neuronal and cognitive function. These results provide strong preclinical validation of this framework, reinforcing the concept that lithium deficiency may be pathogenic and that restoring physiological lithium levels could serve as preventive therapy. The model also incorporates viral contributions (e.g., HSV-1, EBV) as triggers of chronic inflammation and amyloid pathology, offering a more comprehensive view of disease initiation. Importantly, it emphasizes synergy between antioxidants and TMS, highlighting avenues for multimodal prevention. These findings underscore the role of inflammation as both a driver and a modifiable factor in neurodegeneration. Lithium’s anti-inflammatory effects, coupled with biomarker monitoring (e.g., YKL-40, sTREM2), may allow targeted and personalized preventive strategies. We acknowledge limitations, including the need for improved biomarker specificity and sensitivity, inconsistent outcomes of antioxidant trials, accessibility and cost of TMS, and lithium’s therapeutic window. Nonetheless, by reframing AD and PD as preventable rather than inevitable, this framework highlights a proactive strategy that integrates molecular mechanisms, biomarkers, and multimodal therapies with both scientific promise and translational potential.