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JOURNAL ARTICLE
Reduction in Constitutively Activated Auditory Brainstem Microglia in Aging and Alzheimer's Disease.
Tracy Butler, Xiuyuan Wang, Gloria Chiang, Ke Xi, Sumit Niogi, Lidia Glodzik, Yi Li, Qolamreza Ray Razlighi, Liangdong Zhou, Seyed Hani Hojjati, Ilker Ozsahin, Xiangling Mao, Thomas Maloney, Emily Tanzi, Nesrine Rahmouni, Cécile Tissot, Firoza Lussier, Sudhin Shah, Dikoma Shungu, Ajay Gupta, Mony De Leon, P David Mozley, Tharick Pascoal, Pedro Rosa-Neto
BACKGROUND: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. OBJECTIVE: To define age and AD associations of brainstem TSPO PET signal in humans...
April 19, 2024: Journal of Alzheimer's Disease: JAD
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JOURNAL ARTICLE
Yanyan Kong, Cinzia A Maschio, Xuefeng Shi, Fang Xie, Chuantao Zuo, Uwe Konietzko, Kuangyu Shi, Axel Rominger, Jianfei Xiao, Qi Huang, Roger M Nitsch, Yihui Guan, Ruiqing Ni
Reactive astrocytes play an important role in the development of Alzheimer's disease (AD). Here, we aimed to investigate the temporospatial relationships among monoamine oxidase-B, tau and amyloid-β (Aβ), translocator protein, and glucose metabolism by using multitracer imaging in AD transgenic mouse models. Positron emission tomography (PET) imaging with [18 F]SMBT-1 (monoamine oxidase-B), [18 F]florbetapir (Aβ), [18 F]PM-PBB3 (tau), [18 F]fluorodeoxyglucose (FDG), and [18 F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3×Tg mice, and aged-matched wild-type mice...
March 19, 2024: Molecular Neurobiology
#3
JOURNAL ARTICLE
Obada M Alzghool, Richard Aarnio, Jatta S Helin, Saara Wahlroos, Thomas Keller, Markus Matilainen, Junel Solis, Jonathan J Danon, Michael Kassiou, Anniina Snellman, Olof Solin, Juha O Rinne, Merja Haaparanta-Solin
BACKGROUND: P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [11 C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [11 C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [18 F]F-DPA targeting TSPO at the final imaging time point...
March 6, 2024: EJNMMI Research
#4
JOURNAL ARTICLE
Maura Malpetti, Nicolai Franzmeier, Matthias Brendel
This paper provides an overview of the role of neuroinflammation in Alzheimer's disease and other neurodegenerative diseases, highlighting the potential of anti-inflammatory treatments to slow or prevent decline. This research focuses on the use of positron emission tomography (PET) imaging to visualize and quantify molecular brain changes in patients, specifically microglial activation and reactive astrogliosis. We discuss the development and application of several PET radioligands, including first-generation ligands like PK11195 and Ro5-4864, as well as second- and third-generation ligands such as [11C]PBR28, [18F]DPA-714, [18F]GE-180, and [11C]ER176...
2024: Methods in Molecular Biology
#5
JOURNAL ARTICLE
Samantha M Rossano, Aubrey S Johnson, Anna Smith, Galen Ziaggi, Andrew Roetman, Diana Guzman, Amarachukwu Okafor, Julia Klein, Zeljko Tomljanovic, Yaakov Stern, Adam M Brickman, Seonjoo Lee, William C Kreisl, Patrick Lao
INTRODUCTION: Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aβ) precedes local tau and neurodegeneration, resulting in cognitive impairment. METHODS: Florbetaben, PBR28, and MK-6240 PET, T1 magnetic resonance imaging, and cognitive measures were performed in 19 cognitively unimpaired older adults and 22 patients with mild cognitive impairment or mild AD to examine associations among microglia activation, Aβ, tau, and cognition, adjusting for neurodegeneration...
February 1, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#6
JOURNAL ARTICLE
Lauren H Fairley, Amandine Grimm, Steffen A Herff, Anne Eckert
Mitochondrial dysfunction has been widely implicated in the pathogenesis of Alzheimer's disease (AD), with accumulation of damaged and dysfunctional mitochondria occurring early in the disease. Mitophagy, which governs mitochondrial turnover and quality control, is impaired in the AD brain, and strategies aimed at enhancing mitophagy have been identified as promising therapeutic targets. The translocator protein (TSPO) is an outer mitochondrial membrane protein that is upregulated in AD, and ligands targeting TSPO have been shown to exert neuroprotective effects in mouse models of AD...
January 25, 2024: Biochimie
#7
JOURNAL ARTICLE
Gloria Biechele, Boris-Stephan Rauchmann, Daniel Janowitz, Katharina Buerger, Nicolai Franzmeier, Endy Weidinger, Selim Guersel, Sebastian Schuster, Anika Finze, Stefanie Harris, Simon Lindner, Nathalie L Albert, Christian Wetzel, Rainer Rupprecht, Axel Rominger, Carla Palleis, Sabrina Katzdobler, Lena Burow, Carolin Kurz, Mirlind Zaganjori, Lena-Katharina Trappmann, Oliver Goldhardt, Timo Grimmer, Jan Haeckert, Daniel Keeser, Sophia Stoecklein, Estrella Morenas-Rodriguez, Peter Bartenstein, Johannes Levin, Günter U Höglinger, Mikael Simons, Robert Perneczky, Matthias Brendel
BACKGROUND AND OBJECTIVES: 18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer's disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between β-amyloid-accumulation and microglial activation in AD...
January 23, 2024: Journal of Neuroinflammation
#8
JOURNAL ARTICLE
Oliver Cousins, Julia J Schubert, Avinash Chandra, Mattia Veronese, Polena Valkimadi, Byron Creese, Zunera Khan, Ryan Arathimos, Adam Hampshire, Ivana Rosenzweig, Clive Ballard, Anne Corbett, Dag Aasland, Latha Velayudhan, Michael O'Neill, David Collier, Ramla Awais, Kerstin Sander, Erik Årstad, Oliver Howes, Federico Turkheimer, Angela Hodges
BACKGROUND: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile. METHODS: We compared TREM2 p...
November 21, 2023: Journal of Neuroinflammation
#9
JOURNAL ARTICLE
Zhengshi Yang, Sarah J Banks, Aaron R Ritter, Jeffrey L Cummings, Karthik Sreenivasan, Jefferson W Kinney, Jessica K Caldwell, Christina G Wong, Justin B Miller, Dietmar Cordes
BACKGROUND: Emerging evidence suggests a potential causal role of neuroinflammation in Alzheimer's disease (AD). Using positron emission tomography (PET) to image overexpressed 18 kDA translocator protein (TSPO) by activated microglia has gained increasing interest. The uptake of 18F-GE180 TSPO PET was observed to co-localize with inflammatory markers and have a two-stage association with amyloid PET in mice. Very few studies evaluated the diagnostic power of 18F-GE180 PET in AD population and its interpretation in human remains controversial about whether it is a marker of microglial activation or merely reflects disrupted blood-brain barrier integrity in humans...
November 17, 2023: Journal of Alzheimer's Disease: JAD
#10
JOURNAL ARTICLE
Arpit Kumar Pradhan, Tatjana Neumüller, Claudia Klug, Severin Fuchs, Martin Schlegel, Markus Ballmann, Katharina Johanna Tartler, Antoine Pianos, Maria Sanchez Garcia, Philippe Liere, Michael Schumacher, Matthias Kreuzer, Rainer Rupprecht, Gerhard Rammes
Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ). It affects cognition and leads to memory impairment. The mitochondrial translocator protein (TSPO) plays an essential role in maintaining mitochondrial homeostasis and has been implicated in several neuronal disorders or neuronal injuries. Ligands targeting the mitochondrial translocator protein (18 kDa), promote neurosteroidogenesis and may be neuroprotective. To study whether the TSPO ligand XBD173 may exert early neuroprotective effects in AD pathology we investigated the impact of XBD173 on amyloid toxicity and neuroplasticity in mouse models of AD...
October 27, 2023: Translational Psychiatry
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JOURNAL ARTICLE
Azeem Saleem, Syed Imran Ali Shah, Stephen A Mangar, Christopher Coello, Matthew B Wall, Gaia Rizzo, Terry Jones, Patricia M Price
BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. METHODS: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview...
2023: Prostate Cancer
#12
JOURNAL ARTICLE
Miao Zhang, Xiao-Hang Qian, Jialin Hu, Yaoyu Zhang, Xiaozhu Lin, Wangxi Hai, Kuangyu Shi, Xufeng Jiang, Yao Li, Hui-Dong Tang, Biao Li
PURPOSE: Despite the revealed role of immunological dysfunctions in the development and progression of Alzheimer's disease (AD) through animal and postmortem investigations, direct evidence regarding the impact of genetic factors on microglia response and amyloid-β (Aβ) deposition in AD individuals is lacking. This study aims to elucidate this mechanism by integrating transcriptomics and TSPO, Aβ PET imaging in clinical AD cohort. METHODS: We analyzed 85 patients with PET/MR imaging for microglial activation (TSPO, [18 F]DPA-714) and Aβ ([18 F]AV-45) within the prospective Alzheimer's Disease Immunization and Microbiota Initiative Study Cohort (ADIMIC)...
October 6, 2023: European Journal of Nuclear Medicine and Molecular Imaging
#13
JOURNAL ARTICLE
Benjamin B Tournier, Farha Bouteldja, Quentin Amossé, Alekos Nicolaides, Marcelo Duarte Azevedo, Liliane Tenenbaum, Valentina Garibotto, Kelly Ceyzériat, Philippe Millet
An increase in astrocyte reactivity has been described in Alzheimer's disease and seems to be related to the presence of a pro-inflammatory environment. Reactive astrocytes show an increase in the density of the 18 kDa translocator protein (TSPO), but TSPO involvement in astrocyte functions remains poorly understood. The goal of this study was to better characterize the mechanisms leading to the increase in TSPO under inflammatory conditions and the associated consequences. For this purpose, the C6 astrocytic cell line was used in the presence of lipopolysaccharide (LPS) or TSPO overexpression mediated by the transfection of a plasmid encoding TSPO...
August 29, 2023: ACS Omega
#14
JOURNAL ARTICLE
Dominique Gouilly, Anne-Sophie Salabert, Elsa Bertrand, Marie Goubeaud, Hélène Catala, Johanne Germain, Nadéra Ainaoui, Marie Rafiq, Marie Benaiteau, Jasmine Carlier, Leonor Nogueira, Mélanie Planton, Anne Hitzel, Déborah Méligne, Benjamine Sarton, Stein Silva, Béatrice Lemesle, Pierre Payoux, Claire Thalamas, Patrice Péran, Jérémie Pariente
The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer's disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18 F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level...
2023: Frontiers in Neurology
#15
JOURNAL ARTICLE
Emma F Garland, Oliver Dennett, Laurie C Lau, David S Chatelet, Michel Bottlaender, James A R Nicoll, Delphine Boche
The 18kD translocator protein (TSPO) is used as a positron emission tomography (PET) target to quantify neuroinflammation in patients. In Alzheimer's disease (AD), the cerebellum is the pseudo-reference region for comparison with the cerebral cortex due to the absence of AD pathology and lower levels of TSPO. However, using the cerebellum as a pseudo-reference region is debated, with other brain regions suggested as more suitable. This paper aimed to establish the neuroinflammatory differences between the temporal cortex and cerebellar cortex, including TSPO expression...
August 14, 2023: Journal of Neuroinflammation
#16
JOURNAL ARTICLE
Elisa Conti, Denise Grana, Federica Angiulli, Aristotelis Karantzoulis, Ildebrando Appollonio, Carlo Ferrarese, Lucio Tremolizzo
BACKGROUND: Neuroinflammation is one of the cardinal mechanisms of Alzheimer's disease (AD). with amyloid-β (Aβ) playing a critical role by activating microglia to produce soluble inflammatory mediators, including several chemokines. Peripheral monocytes are, therefore, attracted into the central nervous system (CNS), where they change into blood-born microglia and participate in the attempt of removing toxic Aβ species. The translocator protein-18 kDa (TSPO) is a transmembrane protein overexpressed in response to neuroinflammation and known to regulate human monocyte chemotaxis...
August 5, 2023: Journal of Alzheimer's Disease: JAD
#17
JOURNAL ARTICLE
Livia J De Picker, Manuel Morrens, Igor Branchi, Bartholomeus C M Haarman, Tatsuhiro Terada, Min Su Kang, Delphine Boche, Marie-Eve Tremblay, Claire Leroy, Michel Bottlaender, Julie Ottoy
INTRODUCTION: The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity of TSPO PET to identify brain inflammatory processes appears to vary greatly across disorders, disease stages, and applied quantification methods. To advance TSPO PET as a potential biomarker to evaluate brain inflammation and anti-inflammatory therapies, a better understanding of its applicability across disorders is needed...
August 3, 2023: Brain, Behavior, and Immunity
#18
JOURNAL ARTICLE
Anika Finze, Gloria Biechele, Boris-Stephan Rauchmann, Nicolai Franzmeier, Carla Palleis, Sabrina Katzdobler, Endy Weidinger, Selim Guersel, Sebastian Schuster, Stefanie Harris, Julia Schmitt, Leonie Beyer, Johannes Gnörich, Simon Lindner, Nathalie L Albert, Christian H Wetzel, Rainer Rupprecht, Axel Rominger, Adrian Danek, Lena Burow, Carolin Kurz, Maia Tato, Julia Utecht, Boris Papazov, Mirlind Zaganjori, Lena-Katharina Trappmann, Oliver Goldhardt, Timo Grimmer, Jan Haeckert, Daniel Janowitz, Katharina Buerger, Daniel Keeser, Sophia Stoecklein, Olaf Dietrich, Estrella Morenas-Rodriguez, Henryk Barthel, Osama Sabri, Peter Bartenstein, Mikael Simons, Christian Haass, Günter U Höglinger, Johannes Levin, Robert Perneczky, Matthias Brendel
β-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...
July 26, 2023: Molecular Psychiatry
#19
JOURNAL ARTICLE
Adrian Rodriguez-Lopez, Alicia M Torres-Paniagua, Gonzalo Acero, Georgina Díaz, Goar Gevorkian
Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aβ in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies...
July 13, 2023: Journal of Neuroimmunology
#20
JOURNAL ARTICLE
Amina U Syed, Christopher Liang, Krystal K Patel, Rommani Mondal, Vallabhi M Kamalia, Taylor R Moran, Shamiha T Ahmed, Jogeshwar Mukherjee
Increased monoamine oxidase-A (MAO-A) activity in Alzheimer's disease (AD) may be detrimental to the point of neurodegeneration. To assess MAO-A activity in AD, we compared four biomarkers, Aβ plaques, tau, translocator protein (TSPO), and MAO-A in postmortem AD. Radiotracers were [18 F]FAZIN3 for MAO-A, [18 F]flotaza and [125 I]IBETA for Aβ plaques, [124/125 I]IPPI for tau, and [18 F]FEPPA for TSPO imaging. Brain sections of the anterior cingulate (AC; gray matter GM) and corpus callosum (CC; white matter WM) from cognitively normal control (CN, n = 6) and AD ( n = 6) subjects were imaged using autoradiography and immunostaining...
June 28, 2023: International Journal of Molecular Sciences
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