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@ARTICLE{Shapiro:282966,
author = {Shapiro, Noah L and Jones, Peter Simon and Mak, Elijah and
Tsvetanov, Kamen A and Goddard, Julia and Vontobel, Davi S
and Durcan, Robert and Chouliaras, Leonidas and Fryer, Tim
and Hong, Young T and Aigbirhio, Franklin and Heslegrave,
Amanda and Franzmeier, Nicolai and Brendel, Matthias and
Zetterberg, Henrik and O'Brien, John T and Rowe, James B and
Malpetti, Maura},
title = {{I}nflammation {PET} and plasma neurofilament light predict
survival in people with progressive supranuclear palsy.},
journal = {Brain communications},
volume = {7},
number = {6},
issn = {2632-1297},
address = {[Oxford]},
publisher = {Oxford University Press},
reportid = {DZNE-2025-01418},
pages = {fcaf467},
year = {2025},
abstract = {Progressive supranuclear palsy (PSP) is a primary tauopathy
characterized by atrophy and neuroinflammation of the
brainstem, the basal ganglia and, to a lesser degree, the
cortex. This study investigates the association of regional
atrophy (structural MRI), neuroinflammation ([11C]-PK11195
PET), peripheral markers of neurodegeneration [plasma
neurofilament light chain (NfL)] and clinical severity [PSP
rating scale (PSPRS)] with survival in people with PSP.
Fifty-nine people with PSP underwent longitudinal structural
MRI, surviving on average 3.2 years from the first scan (MRI
cohort). Sixteen participants (PET cohort) within this
cohort underwent cross-sectional [11C]-PK11195 PET and blood
sampling for plasma NfL. We applied modality-specific
principal component analyses on imaging data and ran partial
correlations, multivariate regressions and Bayesian models
to evaluate the association between survival and imaging
patterns, clinical severity and plasma NfL. In the PET
cohort, higher levels of localized inflammation in
subcortical regions [rho = -0.49, P = 0.02, Bayes factor
(BF) = 8.07] and plasma NfL (rho = -0.57, P = 0.01, BF =
4.63) were associated with shorter survival, while PSPRS
scores were not significant predictors of survival.
Subcortical atrophy was associated with shorter survival in
the larger cohort (r = -0.38, P = 0.001; β = -0.66, P =
0.001). Spearman's correlations, multivariate regressions
and Bayesian models converged to the same results. Regional
subcortical atrophy is a robust biomarker associated with
survival in people with PSP that can be utilized in
large-scale clinical trials. Translocator protein (TSPO) PET
and plasma NfL offer promising complementary markers for
smaller-scale trials, where they may prove more sensitive
than clinical scores or structural MRI alone. By linking
neuroinflammation to survival, our results also highlight
immunotherapy as a promising avenue for disease-modifying
treatment in PSP.},
keywords = {PET NfL (Other) / neuroinflammation (Other) / progressive
supranuclear palsy (Other) / survival (Other)},
cin = {AG Haass},
ddc = {610},
cid = {I:(DE-2719)1110007},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41416250},
pmc = {pmc:PMC12709281},
doi = {10.1093/braincomms/fcaf467},
url = {https://pub.dzne.de/record/282966},
}