Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Döring F, Trenkwalder C, Schlossmacher MG.
α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study.
Lancet Neurol. 2011 Mar;10(3):230-40.
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Mollenhauer’s study benefits from examining three cohorts, including an autopsy-confirmed cohort with dementia with Lewy bodies (DLB) patients—a group often difficult to distinguish from Alzheimer’s disease (AD) by clinical testing. Measurements of several markers of neurodegenerative disease were made, including α-synuclein, tau, and Aβ1-42. By combining the cerebrospinal fluid measurements for α-synuclein and tau with age, the synucleinopathy group (Parkinson’s disease, DLB, and multiple systems atrophy) could be discriminated from AD and other neurological conditions more clearly than by α-synuclein alone. The α-synuclein differences were confirmed in the autopsy-confirmed cohort of DLB patients.
While able to discriminate between conditions whose primary pathology is α-synuclein and those with other types of pathology, discrimination between different types of synucleinopathy has not been achieved. In many ways, this is as important as being able to differentiate between conditions with differing pathological causes, as the initial stages of the diseases may appear to be very similar, and more accurate diagnoses at an early stage could allow for more targeted treatments.
Discrimination between these conditions could be achieved by a closer analysis of different forms of α-synuclein, focusing on oligomeric α-synuclein, truncated forms, and post-translational modifications, such as phosphorylation and ubiquitination.
An important fact that can be deduced from previous CSF α-synuclein studies is that variation between cohorts, sample preparation, and antibody choice can have an enormous impact on the results. To gain the full clinical benefits from these findings, the results need to be replicated in larger cohorts, including individuals with early diagnoses of mild synucleinopathies and by different laboratories. Further prospective studies which track the changes in α-synuclein throughout disease progression will also be required. This current study provides a basis for future combination studies of CSF biomarkers in synucleinopathies, and it will be exciting to follow how this field progresses in the coming months
Emma L. Jones is funded by the Alzheimer’s Society (Grant Number 112) with support from The Henry Smith Charity.