What is the practical application of alpha-synuclein seed amplification assay CSF testing for the diagnosis and management of Parkinson's disease?

The α-synuclein seed amplification assay (αSyn-SAA) sensitively identifies patients with Parkinson’s disease from cerebrospinal fluid (CSF) samples. A positive αSyn-SAA is proposed to "biologically define" Parkinson’s disease and anchor disease staging. A positive αSyn-SAA identifies aggregated α-synuclein pathology with high sensitivity and specificity, aiding the clinical diagnosis of Parkinson’s disease. However, the test result is qualitative: either positive or negative; it is not quantitative. As such, it doesn't quantify the levels of aggregated α-synuclein in CSF nor how much of the monomeric protein remains. It cannot inform Parkinson’s biology, staging, or pathogenesis nor monitor treatment response. It is a qualitative test (yiel...

I use skin biopsies which have good reported sensitivity and specificity to diagnose PD/DLB and MSA (Gibbons et al., PMID 38506839), and anecdotally able to distinguish between PD/DLB and MSA (Gibbons et al., PMID 36657992).

In my practice, I use skin biopsies when the differential includes tardive parkinsonism, medication-induced parkinsonism (DAT scans can be falsely positive with DARBs), or atypical parkinsonism (as it may help me distinguish a PD/DLB and MSA from CBS or PSP, though often does not change management and there can be co-pathology).