This one is a review, so here are a few highlights:
- No tracer currently exists that can identify deposits of abnormal alpha-synuclein in vivo. All 3 functional scans in use for PD (FD, VMAT2, DAT) attempt instead to quantify presynaptic nigrostriatal dopaminergic neurons by targeting their characteristic proteins
- These scans seem like they’ll be able to help identify presymptomatic patients. In twin studies, twins who were initially unaffected by PD but had low uptake of FD went on to develop clinical signs of PD within 2 years
- But, these scans are less good as a biomarker for clinical trials, at least in their current form, because the motor symptoms of PD keep getting worse even after striatal dopamine is already close to zero, so there is a floor effect.
- Motor symptoms correlate better to the number of cells in the substantia nigra on autopsy. And, it turns out VMAT2 and DAT uptake in the midbrain does correlate with nigral cell counts, so focusing on the midbrain instead of the comma-shape in the basal ganglia is more promising as an imaging biomarker.
- There are some more issues to sort out before these scans will work well as a biomarker, for example how drugs affect the scan.
- These scans don’t differentiate between idiopathic PD and the multiple of Parkinson-plus syndromes like MSA and CBD, but they do differentiate it from essential tremor and drug-induced parkinsonism as well as psychogenic symptoms. BUT, careful because GTP cyclohydrolase deficiency can cause a dopa-responsive parkinsonism that will have a normal scan.
- Unlike the classic teaching that dementia in PD was equally split between cortical synucleinopathy and comorbid Alzheimer’s pathology, studies with PiB (amyloid) scans and autopsy seem to indicate that even though many of these patients do have co-existing amyloid, very few of them have tau pathology, meaning they don’t meet pathologic criteria for diagnosis of AD. In other words, the dementia seems mostly directly related to PD and not to co-existing AD.
And, from the maintenance of separation of correlation and causation department, one of my favorite quotes from a journal article recently (as part of a discussion of manganese-induced parkinsonism in welders):
Alternatively, one could interpret these data to suggest that those with such striatal defects tend to become welders; yet this explanation seems less likely.