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000272854 1001_ $$00000-0001-8923-9656$$aMalpetti, Maura$$b0
000272854 245__ $$aNeuroinflammation Parallels 18F-PI-2620 Positron Emission Tomography Patterns in Primary 4-Repeat Tauopathies.
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000272854 520__ $$aPreclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4-repeat (4R) tauopathies and its role in accelerating disease progression.We tested whether microglial activation (1) progresses in similar spatial patterns as the primary pathology tau spreads across interconnected brain regions, and (2) whether the degree of microglial activation parallels tau pathology spreading.We examined in vivo associations between tau aggregation and microglial activation in 31 patients with clinically diagnosed 4R tauopathies, using 18F-PI-2620 PET and 18F-GE180 (translocator protein [TSPO]) PET. We determined tau epicenters, defined as subcortical brain regions with highest tau PET signal, and assessed the connectivity of tau epicenters to cortical regions of interest using a 3-T resting-state functional magnetic resonance imaging template derived from age-matched healthy elderly controls.In 4R tauopathy patients, we found that higher regional tau PET covaries with elevated TSPO-PET across brain regions that are functionally connected to each other (β = 0.414, P < 0.001). Microglial activation follows similar distribution patterns as tau and distributes primarily across brain regions strongly connected to patient-specific tau epicenters (β = -0.594, P < 0.001). In these regions, microglial activation spatially parallels tau distribution detectable with 18F-PI-2620 PET.Our findings indicate that the spatial expansion of microglial activation parallels tau distribution across brain regions that are functionally connected to each other, suggesting that tau and inflammation are closely interrelated in patients with 4R tauopathies. The combination of in vivo tau and inflammatory biomarkers could therefore support the development of immunomodulatory strategies for disease-modifying treatments in these conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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000272854 650_7 $$2Other$$a4R tauopathies
000272854 650_7 $$2Other$$aPET
000272854 650_7 $$2Other$$aTau
000272854 650_7 $$2Other$$afMRI
000272854 650_7 $$2Other$$ainflammation
000272854 650_7 $$2NLM Chemicals$$atau Proteins
000272854 650_7 $$2NLM Chemicals$$aReceptors, GABA
000272854 650_7 $$2NLM Chemicals$$aTSPO protein, human
000272854 650_2 $$2MeSH$$aHumans
000272854 650_2 $$2MeSH$$aTauopathies: diagnostic imaging
000272854 650_2 $$2MeSH$$aTauopathies: metabolism
000272854 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000272854 650_2 $$2MeSH$$aMale
000272854 650_2 $$2MeSH$$aFemale
000272854 650_2 $$2MeSH$$aAged
000272854 650_2 $$2MeSH$$aMiddle Aged
000272854 650_2 $$2MeSH$$atau Proteins: metabolism
000272854 650_2 $$2MeSH$$aNeuroinflammatory Diseases: diagnostic imaging
000272854 650_2 $$2MeSH$$aNeuroinflammatory Diseases: metabolism
000272854 650_2 $$2MeSH$$aBrain: diagnostic imaging
000272854 650_2 $$2MeSH$$aBrain: metabolism
000272854 650_2 $$2MeSH$$aBrain: pathology
000272854 650_2 $$2MeSH$$aMicroglia: metabolism
000272854 650_2 $$2MeSH$$aReceptors, GABA: metabolism
000272854 7001_ $$aRoemer, Sebastian N$$b1
000272854 7001_ $$aHarris, Stefanie$$b2
000272854 7001_ $$aGross, Mattes$$b3
000272854 7001_ $$0P:(DE-2719)9001652$$aGnoerich, Johannes$$b4$$udzne
000272854 7001_ $$aStephens, Andrew$$b5
000272854 7001_ $$aDewenter, Anna$$b6
000272854 7001_ $$aSteward, Anna$$b7
000272854 7001_ $$aBiel, Davina$$b8
000272854 7001_ $$00000-0001-7116-9741$$aDehsarvi, Amir$$b9
000272854 7001_ $$aWagner, Fabian$$b10
000272854 7001_ $$aMüller, Andre$$b11
000272854 7001_ $$aKoglin, Norman$$b12
000272854 7001_ $$0P:(DE-2719)9000882$$aWeidinger, Endy$$b13$$udzne
000272854 7001_ $$0P:(DE-2719)9000852$$aPalleis, Carla$$b14$$udzne
000272854 7001_ $$0P:(DE-2719)9001160$$aKatzdobler, Sabrina$$b15$$udzne
000272854 7001_ $$aRupprecht, Rainer$$b16
000272854 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b17$$udzne
000272854 7001_ $$0P:(DE-2719)9001808$$aRauchmann, Boris Stephan$$b18$$udzne
000272854 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b19$$udzne
000272854 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b20$$udzne
000272854 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b21
000272854 7001_ $$aFranzmeier, Nicolai$$b22
000272854 773__ $$0PERI:(DE-600)2041249-6$$a10.1002/mds.29924$$gVol. 39, no. 9, p. 1480 - 1492$$n9$$p1480 - 1492$$tMovement disorders$$v39$$x0885-3185$$y2024
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