Author(s)
Ayesha Awwal
Research advisor: Dr. Tiffany Hensely-McBain
Affiliation(s)
Touro College of Osteopathic Medicine - Great Falls, Montana
Abstract:
Helminth infections are an overlooked but emerging domestic health concern in the United States, particularly in regions with poor sanitation and environmental exposure. While these organisms primarily sequester and mature within the nutrient-rich enteric tract, growing evidence suggests that certain species of helminths, including Toxocara canis, can migrate beyond the gastrointestinal tract and contribute to central nervous system (CNS) pathology. This review explores the hypothesis that helminth-induced immunomodulation and neuroinvasion promote neuroinflammation and synaptic dysregulation, potentially accelerating the progression of Alzheimer’s disease (AD) and cognitive decline. A systematic evaluation of peer-reviewed literature and public health data was conducted to examine mechanisms of helminth neuroinvasion, host immune responses, and downstream neurological effects. Studies implementing murine models and translational data were analyzed to identify shared mechanistic routes linking helminth infection to neurodegenerative processes. Therapeutic interventions targeting both parasitic load and inflammatory cascades were also reviewed. Helminth infections demonstrate a propensity for CNS infiltration, with Toxocara canis showing preferential localization in brain tissue and associated with structural damage. These infections trigger significant transcriptional dysregulation in critical pathways involved in cholesterol metabolism, apoptosis, and amyloid processing, all of which are key factors linked to AD pathogenesis. Additionally, helminth-associated activation of microglia and modulation of macrophage phenotypes contribute to persistent neuroinflammation and impairment of synaptic proteins, such as EAAT2 and GABA_Aa1, compromising neuronal signalling. Behavioral studies in murine models further revealed deficits in motor function, memory, and cognition. Therapeutic interventions, such as albendazole and artemether, show promising reductions of infectious burden by preserving neural morphology and mitigating neuroinflammation. Helminth-induced neuroinflammation represents an emerging factor in neurodegenerative diseases. By linking gastrointestinal infections to CNS immune dysregulation and synaptic damage, this work highlights a potential mechanistic pathway connecting parasitic neuroinvasion to cognitive decline and AD. These results may guide further investigation into helminth-associated neurodegeneration and facilitate the exploration of targeted antiparasitic and immunomodulatory therapies as viable strategies for treatment and prevention, particularly in medically underserved and high-risk populations in the United States.