Biomarkers of Parkinson's disease and Dementia with Lewy bodies

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are progressive and disabling neurodegenerative disorders, in which signs and symptoms overlap with each other and with other neurodegenerative conditions. Currently, diagnosis, measurement of progression, and response to therapeutic intervention rely upon clinical observation. However, there remains a critical need for validated biomarkers in each of these areas. A definitive diagnostic test would improve clinical management and enrollment into clinical trials. An objective measure of progression is vitally important in identifying neuroprotective interventions. Biomarkers may also provide insight into pathogenesis, and might therefore suggest possible novel targets for therapeutic intervention. In addition, certain biomarkers might be of use in monitoring the biochemical and physiological effects of therapeutic interventions. Development of diagnostic biomarkers has focused until recently upon imaging techniques based upon measuring loss of dopamine neurons. Additionally, advances in understanding the genetic contribution to neurodegenerative disorders, in particular in PD, have identified multiple causative genes and risk factors that in some cases may help estimate PD risk. However, recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid (CSF) tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB.

► PD, PDD and DLB overlap clinically and are challenging to diagnose in early disease.
► Genetic, biochemical and imaging biomarkers may help distinguish these conditions and provide earlier diagnosis.
► Genetic PD risk loci include MAPT, SNCA, HLA-DRB5, BST1, GAK, and LRRK2.
► Promising approaches: α-synuclein and DJ-1 measurement, “omics” analysis, inflammatory and oxidative stress markers.