To integrate recent evidence on genetic susceptibility and environmental factors implicated in Dementia with Lewy Bodies (DLB) and explore the biological mechanisms linking these domains, including lipid metabolism and neuroinflammatory responses.
Key Findings:
DLB is characterized by cognitive decline, neuropsychiatric symptoms, and parkinsonism, with α-synuclein pathology as a hallmark.
Genetic studies identify key risk loci (APOE, GBA, SNCA) that influence lipid metabolism, lysosomal function, and neuroinflammatory responses.
Environmental exposures (pesticides, air pollution, heavy metals) are linked to α-synuclein aggregation and neuroinflammation.
Current data suggest a framework where genetic background constrains biological vulnerability, while environmental factors modulate disease expression and heterogeneity.
Interpretation:
DLB is a heterogeneous disorder influenced by both genetic predispositions and environmental factors, with complex interactions that significantly affect disease manifestation.
Limitations:
The review is not a formal systematic review, which may limit comprehensiveness and the ability to generalize findings.
Many findings are extrapolated from Parkinson's disease due to a scarcity of DLB-specific studies, which may lead to incomplete understanding.
Conclusion:
Further research is needed to refine understanding of DLB-specific genetic and environmental factors, particularly focusing on lipid metabolism and neuroinflammatory pathways, to improve clinical insights and therapeutic strategies.
