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@ARTICLE{Malpetti:272854,
author = {Malpetti, Maura and Roemer, Sebastian N and Harris,
Stefanie and Gross, Mattes and Gnoerich, Johannes and
Stephens, Andrew and Dewenter, Anna and Steward, Anna and
Biel, Davina and Dehsarvi, Amir and Wagner, Fabian and
Müller, Andre and Koglin, Norman and Weidinger, Endy and
Palleis, Carla and Katzdobler, Sabrina and Rupprecht, Rainer
and Perneczky, Robert and Rauchmann, Boris Stephan and
Levin, Johannes and Höglinger, Günter U and Brendel,
Matthias and Franzmeier, Nicolai},
title = {{N}euroinflammation {P}arallels 18{F}-{PI}-2620 {P}ositron
{E}mission {T}omography {P}atterns in {P}rimary 4-{R}epeat
{T}auopathies.},
journal = {Movement disorders},
volume = {39},
number = {9},
issn = {0885-3185},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2024-01272},
pages = {1480 - 1492},
year = {2024},
abstract = {Preclinical, 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.},
keywords = {Humans / Tauopathies: diagnostic imaging / Tauopathies:
metabolism / Positron-Emission Tomography: methods / Male /
Female / Aged / Middle Aged / tau Proteins: metabolism /
Neuroinflammatory Diseases: diagnostic imaging /
Neuroinflammatory Diseases: metabolism / Brain: diagnostic
imaging / Brain: metabolism / Brain: pathology / Microglia:
metabolism / Receptors, GABA: metabolism / 4R tauopathies
(Other) / PET (Other) / Tau (Other) / fMRI (Other) /
inflammation (Other) / tau Proteins (NLM Chemicals) /
Receptors, GABA (NLM Chemicals) / TSPO protein, human (NLM
Chemicals)},
cin = {Clinical Research (Munich) / AG Haass / AG Höglinger},
ddc = {610},
cid = {I:(DE-2719)1111015 / I:(DE-2719)1110007 /
I:(DE-2719)1110002},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39022835},
doi = {10.1002/mds.29924},
url = {https://pub.dzne.de/record/272854},
}