CSF α-synuclein as a diagnostic biomarker for Parkinson disease and related dementias

Abstract

Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB) are neurodegenerative diseases with a shared pathologic substrate, intraneuronal inclusions of Lewy bodies and Lewy neurites incorporating abnormal aggregates of α-synuclein. Neuroimaging biomarkers, particularly PET and SPECT ligands binding to the dopamine transporter, combined with operationalized clinical criteria can achieve good sensitivity and specificity for the diagnosis of PD, PDD, and DLB.1 However, a CSF biomarker linked to disease pathology may further contribute to diagnostic accuracy, and would be particularly valuable in settings where sophisticated neuroimaging is not available. Perhaps more importantly, a biomarker more closely related to α-synuclein pathology would be invaluable for the development and evaluation of putative disease-modifying therapies in clinical trials. Encouragingly, preliminary results indicate that α-synuclein can be measured in CSF2,–,4 but not all available antibodies are specific to α-synuclein; furthermore, it is not conclusive whether there are consistent PD or DLB-associated changes in total α-synuclein compared to age-matched controls. Of particular note, changes in total α-synuclein have also been reported in Alzheimer disease (AD) compared …