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000307310 1001_ $$00000-0002-7786-2747$$aShapiro, Noah L$$b0
000307310 245__ $$aInflammation PET and plasma neurofilament light predict survival in people with progressive supranuclear palsy.
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000307310 520__ $$aProgressive 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.
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000307310 650_7 $$2Other$$aPET NfL
000307310 650_7 $$2Other$$aneuroinflammation
000307310 650_7 $$2Other$$aprogressive supranuclear palsy
000307310 650_7 $$2Other$$asurvival
000307310 7001_ $$aJones, Peter Simon$$b1
000307310 7001_ $$00000-0002-6437-8024$$aMak, Elijah$$b2
000307310 7001_ $$aTsvetanov, Kamen A$$b3
000307310 7001_ $$aGoddard, Julia$$b4
000307310 7001_ $$aVontobel, Davi S$$b5
000307310 7001_ $$00000-0001-9870-0117$$aDurcan, Robert$$b6
000307310 7001_ $$00000-0002-3052-3879$$aChouliaras, Leonidas$$b7
000307310 7001_ $$aFryer, Tim$$b8
000307310 7001_ $$aHong, Young T$$b9
000307310 7001_ $$aAigbirhio, Franklin$$b10
000307310 7001_ $$aHeslegrave, Amanda$$b11
000307310 7001_ $$00000-0001-9736-2283$$aFranzmeier, Nicolai$$b12
000307310 7001_ $$00000-0002-9247-2843$$aBrendel, Matthias$$b13
000307310 7001_ $$aZetterberg, Henrik$$b14
000307310 7001_ $$00000-0002-0837-5080$$aO'Brien, John T$$b15
000307310 7001_ $$aRowe, James B$$b16
000307310 7001_ $$00000-0001-8923-9656$$aMalpetti, Maura$$b17
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