Progressive Supranuclear Palsy (PSP) is a clinically heterogeneous 4-repeat (4R)-tauopathy marked by variable progression and phenotypic diversity. We examined the distribution of high-molecular-weight tau (HMW-tau) species and 4R-tau seeding capacity across 25 PSP cases and 20 brain regions. HMW-tau levels varied regionally, with the temporal and motor cortices exhibiting the highest abundance. Using size-exclusion chromatography (SEC) and 4R-tau seed amplification assays (SAAs), we identified that HMW-tau fractions exhibit the greatest seeding activity. Proteomic and spatial transcriptomic analyses of the primary motor cortex revealed dysregulated adaptive immunity and metabolic pathways in high-seeder cases. Neuropathological clustering confirmed distinct profiles associated with tau seeding activity. These findings suggest that evaluating tau seeding capacity may offer valuable insights into the heterogeneity of PSP and its underlying molecular drivers.
import lamindb as ln
import spatialdata as sd
coll = ln.Collection.get(key="geo-gse302160")
coll.ordered_artifacts.df() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}
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