Bridging Molecular Genetics and Biomarkers in Lewy Body and Related Disorders

Abstract

Recent advances have been made in defining the genetic and molecular basis of dementia with Lewy bodies (DLBs) and related neurodegenerative disorders such as Parkinson's disease (PD) and Parkinson's disease dementia (PDD) which comprise the spectrum of “Lewy body disorders” (LBDs). The genetic alterations and underlying disease mechanisms in the LBD overlap substantially, suggesting common disease mechanisms. As with the other neurodegenerative dementias, early diagnosis in LBD or even identification prior to symptom onset is key to developing effective therapeutic strategies, but this is dependent upon the development of robust, specific, and sensitive biomarkers as diagnostic tools and therapeutic endpoints. Recently identified mutations in the synucleins and other relevant genes in PD and DLB as well as related biomolecular pathways suggest candidate markers from biological fluids and imaging modalities that reflect the underlying disease mechanisms. In this context, several promising biomarkers for the LBD have already been identified and examined, while other intriguing possible candidates have recently emerged. Challenges remain in defining their correlation with pathological processes and their ability to detect DLB and related disorders, and perhaps a combined array of biomarkers may be needed to distinguish various LBDs.