Big News: PET Scan Detects Alpha-synuclein in Those with MSA (Alzforum)


Here’s an excerpt from an Alzforum article on this big research news:

 

For the first time, scientists have detected α-synuclein aggregates lurking in the brains of the living. This thanks to 18F-ACI-12589, a new tracer developed by AC Immune in Lausanne, Switzerland. Presented at AD/PD 2022…the first PET scans using the tracer showed uptake in the cerebellar white matter of people with multiple system atrophy (MSA). … Alas, PET signals were undetectable in the brains of people with other synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, despite selective binding of the tracer to postmortem brain samples of people who had died with those disorders.


This tracer was studied in both types of MSA — MSA-cerebellar (MSA-c) and MSA-parkinsonian (MSA-p).  Even in the MSA-p subtype, the cerebellum is affected by alpha-synuclein pathology.  The Alzforum article notes:  

Though people with either MSA subtype evinced binding in these regions, it was greater, on average, in those with MSA-c. Tracer uptake in cerebellar white matter completely distinguished people with MSA from controls and from those with other synucleinopathies, none of whom had significant uptake in this region.


These disorders are all synucleinopathies — multiple system atrophy (MSA), Parkinson’s disease (PD), Lewy body dementia (LBD), and dementia with Lewy bodies (DLB).  It is interesting that this new PET tracer only showed uptake in MSA.  The Alzforum article asks this question:   

Why the tracer fell short in people with other synucleinopathies remains unclear. [Reearchers] suspect it is because they have far fewer deposits, and tracer binding may have been too weak to detect them. Differences in α-synuclein fibril conformation, or in where the aggregates are in the brain, could also contribute.


The Alzforum article explained the decades-long difficulties in developing an alpha-synuclein tracer:  

The road to synuclein imaging has been long and strewn with obstacles. Compared to amyloid plaques and neurofibrillary tangles, α-synuclein fibrils exist in low concentrations in the human brain. This, combined with its intracellular location and myriad structural conformations, makes α-synuclein a tough target for PET tracers.

See the full article on Alzforum.
In First for the Field, α-Synuclein PET. Only for Multiple System Atrophy
AlzForum
26 Mar 2022

This is exciting news!