Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies
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Published:2023-07-26
Issue:10
Volume:28
Page:4438-4450
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ISSN:1359-4184
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Container-title:Molecular Psychiatry
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language:en
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Short-container-title:Mol Psychiatry
Author:
Finze Anika, Biechele Gloria, Rauchmann Boris-Stephan, Franzmeier NicolaiORCID, Palleis Carla, Katzdobler Sabrina, Weidinger Endy, Guersel SelimORCID, Schuster Sebastian, Harris Stefanie, Schmitt Julia, Beyer Leonie, Gnörich Johannes, Lindner Simon, Albert Nathalie L., Wetzel Christian H.ORCID, Rupprecht RainerORCID, Rominger AxelORCID, Danek Adrian, Burow Lena, Kurz Carolin, Tato Maia, Utecht Julia, Papazov Boris, Zaganjori Mirlind, Trappmann Lena-Katharina, Goldhardt Oliver, Grimmer Timo, Haeckert Jan, Janowitz Daniel, Buerger Katharina, Keeser DanielORCID, Stoecklein Sophia, Dietrich OlafORCID, Morenas-Rodriguez Estrella, Barthel Henryk, Sabri OsamaORCID, Bartenstein Peter, Simons Mikael, Haass Christian, Höglinger Günter U.ORCID, Levin Johannes, Perneczky RobertORCID, Brendel MatthiasORCID
Abstract
Abstractβ-amyloid (Aβ) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer’s disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated. We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, Aβ-, tau-, and perfusion-surrogate-PET, as well as structural MRI. Z-score deviations for 246 brain regions were calculated and biomarker contributions of Aβ (A), tau (T), perfusion (N1), and gray matter atrophy (N2) to microglial activation (TSPO, I) were calculated for each individual subject. Individual ATN-related microglial activation was correlated with clinical performance and CSF soluble TREM2 (sTREM2) concentrations. In typical and atypical AD, regional tau was stronger and more frequently associated with microglial activation when compared to regional Aβ (AD: βT = 0.412 ± 0.196 vs. βA = 0.142 ± 0.123, p < 0.001; AD-CBS: βT = 0.385 ± 0.176 vs. βA = 0.131 ± 0.186, p = 0.031). The strong association between regional tau and microglia reproduced well in primary tauopathies (βT = 0.418 ± 0.154). Stronger individual associations between tau and microglial activation were associated with poorer clinical performance. In patients with 4RT, sTREM2 levels showed a positive association with tau-related microglial activation. Tau pathology has strong regional associations with microglial activation in primary and secondary tauopathies. Tau and Aβ related microglial response indices may serve as a two-dimensional in vivo assessment of neuroinflammation in neurodegenerative diseases.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Psychiatry and Mental health,Molecular Biology
Reference84 articles.
1. Ziegler-Graham K, Brookmeyer R, Johnson E, Arrighi HM. Worldwide variation in the doubling time of Alzheimer’s disease incidence rates. Alzheimers Dement. 2008;4:316–23. 2. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8:595–608. 3. Kovacs GG. Invited review: neuropathology of tauopathies: principles and practice. Neuropathol Appl Neurobiol. 2015;41:3–23. 4. Palleis C, Brendel M, Finze A, Weidinger E, Botzel K, Danek A, et al. Cortical [(18) F]PI-2620 binding differentiates corticobasal syndrome subtypes. Mov Disord. 2021;36:2104–15. 5. Braak H, Braak E. Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol. 1991;1:213–6.
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