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3. A consensus protocol for functional connectivity analysis in the rat brain

Author

Grandjean, Joanes, Desrosiers-Gregoire, Gabriel, Anckaerts, Cynthia, Angeles-Valdez, Diego, Ayad, Fadi, Barrière, David A., Blockx, Ines, Bortel, Aleksandra, Broadwater, Margaret, Cardoso, Beatriz M., Célestine, Marina, Chavez-Negrete, Jorge E., Choi, Sangcheon, Christiaen, Emma, Clavijo, Perrin, Colon-Perez, Luis, Cramer, Samuel, Daniele, Tolomeo, Dempsey, Elaine, Diao, Yujian, Doelemeyer, Arno, Dopfel, David, Dvořáková, Lenka, Falfán-Melgoza, Claudia, Fernandes, Francisca F., Fowler, Caitlin F., Fuentes-Ibañez, Antonio, Garin, Clément M., Gelderman, Eveline, Golden, Carla E. M., Guo, Chao C. G., Henckens, Marloes J. A. G., Hennessy, Lauren A., Herman, Peter, Hofwijks, Nita, Horien, Corey, Ionescu, Tudor M., Jones, Jolyon, Kaesser, Johannes, Kim, Eugene, Lambers, Henriette, Lazari, Alberto, Lee, Sung-Ho, Lillywhite, Amanda, Liu, Yikang, Liu, Yanyan Y., López -Castro, Alejandra, López-Gil, Xavier, Ma, Zilu, MacNicol, Eilidh, Madularu, Dan, Mandino, Francesca, Marciano, Sabina, McAuslan, Matthew J., McCunn, Patrick, McIntosh, Alison, Meng, Xianzong, Meyer-Baese, Lisa, Missault, Stephan, Moro, Federico, Naessens, Daphne M. P., Nava-Gomez, Laura J., Nonaka, Hiroi, Ortiz, Juan J., Paasonen, Jaakko, Peeters, Lore M., Pereira, Mickaël, Perez, Pablo D., Pompilus, Marjory, Prior, Malcolm, Rakhmatullin, Rustam, Reimann, Henning M., Reinwald, Jonathan, Del Rio, Rodrigo Triana, Rivera-Olvera, Alejandro, Ruiz-Pérez, Daniel, Russo, Gabriele, Rutten, Tobias J., Ryoke, Rie, Sack, Markus, Salvan, Piergiorgio, Sanganahalli, Basavaraju G., Schroeter, Aileen, Seewoo, Bhedita J., Selingue, Erwan, Seuwen, Aline, Shi, Bowen, Sirmpilatze, Nikoloz, Smith, Joanna A. B., Smith, Corrie, Sobczak, Filip, Stenroos, Petteri J., Straathof, Milou, Strobelt, Sandra, Sumiyoshi, Akira, Takahashi, Kengo, Torres-García, Maria E., Tudela, Raul, van den Berg, Monica, van der Marel, Kajo, van Hout, Aran T. B., Vertullo, Roberta, Vidal, Benjamin, Vrooman, Roël M., Wang, Victora X., Wank, Isabel, Watson, David J. G., Yin, Ting, Zhang, Yongzhi, Zurbruegg, Stefan, Achard, Sophie, Alcauter, Sarael, Auer, Dorothee P., Barbier, Emmanuel L., Baudewig, Jürgen, Beckmann, Christian F., Beckmann, Nicolau, Becq, Guillaume J. P. C., Blezer, Erwin L. A., Bolbos, Radu, Boretius, Susann, Bouvard, Sandrine, Budinger, Eike, Buxbaum, Joseph D., Cash, Diana, Chapman, Victoria, Chuang, Kai-Hsiang, Ciobanu, Luisa, Coolen, Bram F., Dalley, Jeffrey W., Dhenain, Marc, Dijkhuizen, Rick M., Esteban, Oscar, Faber, Cornelius, Febo, Marcelo, Feindel, Kirk W., Forloni, Gianluigi, Fouquet, Jérémie, Garza-Villarreal, Eduardo A., Gass, Natalia, Glennon, Jeffrey C., Gozzi, Alessandro, Gröhn, Olli, Harkin, Andrew, Heerschap, Arend, Helluy, Xavier, Herfert, Kristina, Heuser, Arnd, Homberg, Judith R., Houwing, Danielle J., Hyder, Fahmeed, Ielacqua, Giovanna Diletta, Jelescu, Ileana O., Johansen-Berg, Heidi, Kaneko, Gen, Kawashima, Ryuta, Keilholz, Shella D., Keliris, Georgios A., Kelly, Clare, Kerskens, Christian, Khokhar, Jibran Y., Kind, Peter C., Langlois, Jean-Baptiste, Lerch, Jason P., López-Hidalgo, Monica A., Manahan-Vaughan, Denise, Marchand, Fabien, Mars, Rogier B., Marsella, Gerardo, Micotti, Edoardo, Muñoz-Moreno, Emma, Near, Jamie, Niendorf, Thoralf, Otte, Willem M., Pais-Roldán, Patricia, Pan, Wen-Ju, Prado-Alcalá, Roberto A., Quirarte, Gina L., Rodger, Jennifer, Rosenow, Tim, Sampaio-Baptista, Cassandra, Sartorius, Alexander, Sawiak, Stephen J., Scheenen, Tom W. J., Shemesh, Noam, Shih, Yen-Yu Ian, Shmuel, Amir, Soria, Guadalupe, Stoop, Ron, Thompson, Garth J., Till, Sally M., Todd, Nick, Van Der Linden, Annemie, van der Toorn, Annette, van Tilborg, Geralda A. F., Vanhove, Christian, Veltien, Andor, Verhoye, Marleen, Wachsmuth, Lydia, Weber-Fahr, Wolfgang, Wenk, Patricia, Yu, Xin, Zerbi, Valerio, Zhang, Nanyin, Zhang, Baogui B., Zimmer, Luc, Devenyi, Gabriel A., Chakravarty, M. Mallar, and Hess, Andreas

Published
2023
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7. Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Author

Grandjean, Joanes, Canella, Carola, Anckaerts, Cynthia, Ayrancı, Gülebru, Bougacha, Salma, Bienert, Thomas, Buehlmann, David, Coletta, Ludovico, Gallino, Daniel, Gass, Natalia, Garin, Clément M., Nadkarni, Nachiket Abhay, Hübner, Neele S., Karatas, Meltem, Komaki, Yuji, Kreitz, Silke, Mandino, Francesca, Mechling, Anna E., Sato, Chika, Sauer, Katja, Shah, Disha, Strobelt, Sandra, Takata, Norio, Wank, Isabel, Wu, Tong, Yahata, Noriaki, Yeow, Ling Yun, Yee, Yohan, Aoki, Ichio, Chakravarty, M. Mallar, Chang, Wei-Tang, Dhenain, Marc, von Elverfeldt, Dominik, Harsan, Laura-Adela, Hess, Andreas, Jiang, Tianzi, Keliris, Georgios A., Lerch, Jason P., Meyer-Lindenberg, Andreas, Okano, Hideyuki, Rudin, Markus, Sartorius, Alexander, Van der Linden, Annemie, Verhoye, Marleen, Weber-Fahr, Wolfgang, Wenderoth, Nicole, Zerbi, Valerio, and Gozzi, Alessandro

Published
2020
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11. Encephalopathy induced by Alzheimer brain inoculation in a non-human primate

Author

Gary, Charlotte, Lam, Suzanne, Hérard, Anne-Sophie, Koch, James E., Petit, Fanny, Gipchtein, Pauline, Sawiak, Stephen J., Caillierez, Raphaëlle, Eddarkaoui, Sabiha, Colin, Morvane, Aujard, Fabienne, Deslys, Jean-Philippe, French Neuropathology Network, Brouillet, Emmanuel, Buée, Luc, Comoy, Emmanuel E., Pifferi, Fabien, Picq, Jean-Luc, and Dhenain, Marc

Published
2019
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13. Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer’s disease

Author

Ceyzériat, Kelly, Ben Haim, Lucile, Denizot, Audrey, Pommier, Dylan, Matos, Marco, Guillemaud, Océane, Palomares, Marie-Ange, Abjean, Laurene, Petit, Fanny, Gipchtein, Pauline, Gaillard, Marie-Claude, Guillermier, Martine, Bernier, Sueva, Gaudin, Mylène, Aurégan, Gwenaëlle, Joséphine, Charlène, Déchamps, Nathalie, Veran, Julien, Langlais, Valentin, Cambon, Karine, Bemelmans, Alexis P, Baijer, Jan, Bonvento, Gilles, Dhenain, Marc, Deleuze, Jean-François, Oliet, Stéphane H R, Brouillet, Emmanuel, Hantraye, Philippe, Carrillo-de Sauvage, Maria-Angeles, Olaso, Robert, Panatier, Aude, and Escartin, Carole

Published
2018
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17. Intrahippocampal Inoculation of Aβ 1–42 Peptide in Rat as a Model of Alzheimer's Disease Identified MicroRNA-146a-5p as Blood Marker with Anti-Inflammatory Function in Astrocyte Cells.

Author

Aquino, Ruth, de Concini, Vidian, Dhenain, Marc, Lam, Suzanne, Gosset, David, Baquedano, Laura, Forero, Manuel G., Menuet, Arnaud, Baril, Patrick, and Pichon, Chantal

Subjects
ALZHEIMER'S disease, PEPTIDES, CELL physiology, ANIMAL disease models, GENE expression, AMYLOID beta-protein precursor
Abstract

Circulating microRNAs (miRNAs) have aroused a lot of interest as reliable blood diagnostic biomarkers of Alzheimer's disease (AD). Here, we investigated the panel of expressed blood miRNAs in response to aggregated Aβ1–42 peptides infused in the hippocampus of adult rats to mimic events of the early onset of non-familial AD disorder. Aβ1–42 peptides in the hippocampus led to cognitive impairments associated with an astrogliosis and downregulation of circulating miRNA-146a-5p, -29a-3p, -29c-3p, -125b-5p, and-191-5p. We established the kinetics of expression of selected miRNAs and found differences with those detected in the APPswe/PS1dE9 transgenic mouse model. Of note, miRNA-146a-5p was exclusively dysregulated in the Aβ-induced AD model. The treatment of primary astrocytes with Aβ1–42 peptides led to miRNA-146a-5p upregulation though the activation of the NF-κB signaling pathway, which in turn downregulated IRAK-1 but not TRAF-6 expression. As a consequence, no induction of IL-1β, IL-6, or TNF-α was detected. Astrocytes treated with a miRNA-146-5p inhibitor rescued IRAK-1 and changed TRAF-6 steady-state levels that correlated with the induction of IL-6, IL-1β, and CXCL1 production, indicating that miRNA-146a-5p operates anti-inflammatory functions through a NF-κB pathway negative feedback loop. Overall, we report a panel of circulating miRNAs that correlated with Aβ1–42 peptides' presence in the hippocampus and provide mechanistic insights into miRNA-146a-5p biological function in the development of the early stage of sporadic AD. [ABSTRACT FROM AUTHOR]

Published
2023
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24. CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer’s disease

Author

Djelti, Fathia, Braudeau, Jerome, Hudry, Eloise, Dhenain, Marc, Varin, Jennifer, Bièche, Ivan, Marquer, Catherine, Chali, Farah, Ayciriex, Sophie, Auzeil, Nicolas, Alves, Sandro, Langui, Dominique, Potier, Marie-Claude, Laprevote, Olivier, Vidaud, Michel, Duyckaerts, Charles, Miles, Richard, Aubourg, Patrick, and Cartier, Nathalie

Published
2015
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26. Commission Relations Homme-Animaux de l’Académie Vétérinaire de France: Etude critique de la proposition de loi n° 3661 visant à renforcer la lutte contre la maltraitance animale

Author

Milhaud, Claude, Rosolen, Serge, LeBars, Daniel, Rousseau, Jean-Paul, Dhenain, Marc, Deregnaucourt, Jean, Maurin-Blanchet, Henri, Medaille, Christine, Baussier, Michel, Deputte, Bertrand L, Kahn, Jean, Vanelle, Anne-Marie, Hugot, Jean-Pierre, Jegou, Jean-Pierre, and Fabre, Agnès

Published
2021
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27. Effect of Alzheimer’s disease‐related β‐amyloid peptide conformations in transgenic mouse models of β‐amyloidosis

Author

Célestine, Marina, Jacquier‐sarlin, Muriel, Borel, Eve, Herard, Anne‐sophie, Buisson, Alain, Dhenain, Marc, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Abstract

International audience; Background: Alzheimer's disease (AD) brain dysfunctions are not exclusively related to amyloid plaques occurence, but are thought to start much earlier, presumably due to soluble pathological forms of b-amyloid peptide (Aβ). Indeed Aβ oligomers induce synaptic dysfunctions that cause cognitive decline, exacerbate tau pathology[1] and influence neuronal networks[2]. Although mutation-induced phenotypes are identified in AD patients, the in vivo effects of different Aβ variants are poorly understood. Here we characterized the effects of different Aβ variants in a transgenic mouse modelto provide deeper insight of transconformational processes and the subsequent alterations. Deciphering Ab profiles would help in developing new diagnostic and therapeutic approaches.References: (1) Delacourte et al., Experimental Gerontology, 2002. (2) Bero et al., Journal of Neuroscience, 2012.

Published
2020

28. Heterogeneity of Alzheimer’s disease: Insight from a novel mouse model of amyloid and tau lesions based on the inoculation of human brain preparations

Author

Lam, Suzanne, Boluda, Susana, Herard, Anne‐sophie, Petit, Fanny, Duyckaerts, Charles, Delatour, Benoit, Haïk, Stéphane, Dhenain, Marc, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Abstract

International audience; Background: A major challenge in clinical research is to better understand the heterogeneity of AD. Indeed, AD is heterogeneous regarding its origin, neuropathology and clinical expressions. While classical sporadic forms of AD (clAD) evolve over approximately 10 years, the "rapidly progressive form of AD" (rAD) is a non-genetic aggressive form associated with a rapid clinical decline that evolves over approximately 2 years (Schmidt et al., Arch Neurol. 2011). Several studies have shown that the experimental inoculation of brain samples with Aβ- and/or tau pathology into transgenic (tg) mouse models overexpressing mutant human APP or tau promotes either Aβ or tau aggregation in the brain of the recipient animal (Gary et al., Acta Neuropathol Com. 2019). The phenotype of the inoculated brains is moreover reproduced in the recipient host (Watts et al., PNAS. 2014). The aim of this work was to study the impact of the inoculations of rAD versus clAD-human brain preparations in tg mice mouse models of β-amyloidosis to explore the mechanisms associated to AD heterogeneity.

Published
2020

29. Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains

Author

Herard, Anne-Sophie, Petit, Fanny, Gary, Charlotte, Guillermier, Martine, Boluda, Susana, Garin, Clément, Lam, Suzanne, Dhenain, Marc, Letournel, Franck, Martin-Negrier, Marie-Laure, Faisant, Maxime, Godfraind, Catherine, Maurage, Claude-Alain, Deramecourt, Vincent, Duchesne, Mathilde, Meyronnet, David, Maues De Paula, André, Rigau, Valérie, Burel-Vandenbos, Fanny, Duyckaerts, Charles, Seilhean, Danielle, Plu, Isabelle, Milin, Serge, Chiforeanu, Dan Christian, Laquerriere, Annie, Lannes, Béatrice, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie Raymond Escourolle, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), France-Alzheimer Association, Fondation Vaincre Alzheimer, CEA bottom-up program, NeurATRIS - ANR-11-INBS-0011, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut des Neurosciences de Montpellier (INM)

Subjects
Genetically modified mouse, Pathology, medicine.medical_specialty, Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Iatrogenic Disease, Mice, Transgenic, Plaque, Amyloid, Endogeny, Context (language use), Hippocampal formation, β-amyloid pathology, Hippocampus, lcsh:RC346-429, Pathology and Forensic Medicine, Lesion, Amyloid beta-Protein Precursor, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Presenilin-1, medicine, Animals, Humans, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, Tissue Extracts, Chemistry, Research, Amyloidosis, Brain, Human brain, Alzheimer's disease, medicine.disease, Immunohistochemistry, Disease Models, Animal, medicine.anatomical_structure, Neurology (clinical), medicine.symptom, Aβ transmission, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract

In humans, iatrogenic transmission of cerebral amyloid-β (Aβ)-amyloidosis is suspected following inoculation of pituitary-derived hormones or dural grafts presumably contaminated with Aβ proteins as well as after cerebral surgeries. Experimentally, intracerebral inoculation of brain homogenate extracts containing misfolded Aβ can seed Aβ deposition in transgenic mouse models of amyloidosis or in non-human primates. The transmission of cerebral Aβ is governed by the host and by the inoculated samples. It is critical to better characterize the propensities of different hosts to develop Aβ deposition after contamination by an Aβ-positive sample as well as to better assess which biological samples can transmit this lesion. Aβ precursor protein (huAPPwt) mice express humanized non-mutated forms of Aβ precursor protein and do not spontaneously develop Aβ or amyloid deposits. We found that inoculation of Aβ-positive brain extracts from Alzheimer patients in these mice leads to a sparse Aβ deposition close to the alveus 18 months post-inoculation. However, it does not induce cortical or hippocampal Aβ deposition. Secondary inoculation of apparently amyloid deposit-free hippocampal extracts from these huAPPwt mice to APPswe/PS1dE9 mouse models of amyloidosis enhanced Aβ deposition in the alveus 9 months post-inoculation. This suggests that Aβ seeds issued from human brain samples can persist in furtive forms in brain tissues while maintaining their ability to foster Aβ deposition in receptive hosts that overexpress endogenous Aβ. This work emphasizes the need for high-level preventive measures, especially in the context of neurosurgery, to prevent the risk of iatrogenic transmission of Aβ lesions from samples with sparse amyloid markers.

Published
2020

37. Voxel-Based Statistical Analysis of 3D Immunostained Tissue Imaging

Author

Vandenberghe, Michel, Souedet, Nicolas, Herard, Anne-Sophie, Ayral, Anne-Marie, Letronne, Florent, Balbastre, Yael, Sadouni, Elmahdi, Hantraye, Philippe, Dhenain, Marc, Frouin, Frédérique, Lambert, Jean-Charles, Delzescaux, Thierry, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut d'Imagerie BioMédicale (I2BM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CEA [Fontenay-aux-Roses] (UGRA / SETA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire d'imagerie fonctionnelle [CHU Pitié-Salpétriêre] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Imagerie et Simulation pour le Contrôle (DISC), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Laboratoire d'imagerie fonctionnelle [Paris] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), and Hérard, Anne-Sophie

Subjects
[SDV] Life Sciences [q-bio], voxel-based, [SDV]Life Sciences [q-bio], immunohistochemistry, rodent, microscopy, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Neuroscience, Original Research, 3D
Abstract

International audience; Recently developed techniques to visualize immunostained tissues in 3D and in large samples have expanded the scope of microscopic investigations at the level of the whole brain. Here, we propose to adapt voxel-based statistical analysis to 3D high-resolution images of the immunostained rodent brain. The proposed approach was first validated with a simulation dataset with known cluster locations. Then, it was applied to characterize the effect of ADAM30, a gene involved in the metabolism of the amyloid precursor protein, in a mouse model of Alzheimer's disease. This work introduces voxel-based analysis of 3D immunostained microscopic brain images and, therefore, opens the door to localized whole-brain exploratory investigation of pathological markers and cellular alterations.

Published
2018

40. Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of amyloidosis and in human Alzheimer’s disease brains

Author

Dudeffant, Clémence, Vandesquille, Matthias, Herbert, Kelly, Garin, Clément M., Alves, Sandro, Blanchard, Véronique, Comoy, Emmanuel E., Petit, Fanny, Dhenain, Marc, Le Roy, Léna, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique (U986), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanofi Aventis R&D [Chilly-Mazarin], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Medicen (Pôle de compétitivité Ile-de-France, TransAl program)Banque Publique d’Investissement (Romane program)France-Alzheimer Association, Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB)

Subjects
Iron, Science, [SDV]Life Sciences [q-bio], Contrast Media, Gadolinium, Mice, Transgenic, Plaque, Amyloid, Amyloidosis, Magnetic Resonance Imaging, Article, [SDV] Life Sciences [q-bio], Disease Models, Animal, Mice, Alzheimer Disease, mental disorders, Animals, Humans, Medicine, Autopsy
Abstract

International audience; Gadolinium (Gd)-stained MRI is based on Gd contrast agent (CA) administration into the brain parenchyma. The strong signal increase induced by Gd CA can be converted into resolution enhancement to record microscopic MR images. Moreover, inhomogeneous distribution of the Gd CA in the brain improves the contrast between different tissues and provides new contrasts in MR images. Gd-stained MRI detects amyloid plaques, one of the microscopic lesions of Alzheimer's disease (AD), in APP SL /PS1 M146L mice or in primates. Numerous transgenic mice with various plaque typologies have been developed to mimic cerebral amyloidosis and comparison of plaque detection between animal models and humans with new imaging methods is a recurrent concern. Here, we investigated detection of amyloid plaques by Gd-stained MRI in five mouse models of amyloidosis (APP SL /PS1 M146L , APP/ PS1 dE9 , APP23, APP SwDI , and 3xTg) presenting with compact, diffuse and intracellular plaques as well as in post mortem human-AD brains. The brains were then evaluated by histology to investigate the impact of size, compactness, and iron load of amyloid plaques on their detection by MRI. We show that Gd-stained MRI allows detection of compact amyloid plaques as small as 25 µm, independently of their iron load, in mice as well as in human-AD brains.

Published
2017

42. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease.

Author

Li, Tengfei, Martin, Elodie, Abada, Yah-se, Boucher, Céline, Cès, Aurélia, Youssef, Ihsen, Fenaux, Grégory, Forand, Yona, Legrand, Annaelle, Nachiket, Nadkarni, Dhenain, Marc, Hermine, Olivier, Dubreuil, Patrice, Delarasse, Cécile, and Delatour, Benoît

Subjects
ALZHEIMER'S disease, TRANSGENIC mice, MAST cells, ALZHEIMER'S patients, SYNAPTOPHYSIN, TREATMENT effectiveness, TRYPTASE, BIOLOGICAL models, RESEARCH, NERVOUS system, ANIMAL experimentation, RESEARCH methodology, COGNITION, PROTEIN precursors, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, MEMBRANE proteins, THIAZOLES, PEPTIDES, MICE, PHARMACODYNAMICS
Abstract

Background: Masitinib is a selective tyrosine kinase inhibitor that modulates mast cells activity. A previous phase II study reported a cognitive effect of masitinib in patients with Alzheimer's disease.Objective: We aimed to shed light on the mode of action of masitinib in Alzheimer's disease.Methods/results: We demonstrated here that chronic oral treatment of APPswe/PSEN1dE9 transgenic mice modeling Alzheimer's disease restored normal spatial learning performance while having no impacts on amyloid-β loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPswe/PSEN1dE9 mice similarly rescued synaptic impairments.Conclusion: These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition. [ABSTRACT FROM AUTHOR]

Published
2020
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43. Sammba-MRI: A Library for Processing SmAll-MaMmal BrAin MRI Data in Python.

Author

Celestine, Marina, Nadkarni, Nachiket A., Garin, Clément M., Bougacha, Salma, and Dhenain, Marc

Subjects
LIBRARY technical services, PYTHON programming language, DATA conversion
Abstract

Small-mammal neuroimaging offers incredible opportunities to investigate structural and functional aspects of the brain. Many tools have been developed in the last decade to analyse small animal data, but current softwares are less mature than the available tools that process human brain data. The Python package Sammba-MRI (SmAll-MaMmal BrAin MRI in Python; http://sammba-mri.github.io) allows flexible and efficient use of existing methods and enables fluent scriptable analysis workflows, from raw data conversion to multimodal processing. [ABSTRACT FROM AUTHOR]

Published
2020
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44. An Automated Open-Source Workflow for Standards-Compliant Integration of Small Animal Magnetic Resonance Imaging Data.

Author

Ioanas, Horea-Ioan, Marks, Markus, Garin, Clément M., Dhenain, Marc, Yanik, Mehmet Fatih, and Rudin, Markus

Subjects
MAGNETIC resonance imaging, WORKFLOW, WORKFLOW management, WORKFLOW software, DATA structures, BRAIN imaging
Abstract

Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons. In small animal magnetic resonance imaging, an overwhelming proportion of data is acquired via the ParaVision software of the Bruker Corporation. The original data structure is predominantly transparent, but fundamentally incompatible with modern pipelines. Additionally, it sources metadata from free-field operator input, which diverges strongly between laboratories and researchers. In this article we present an open-source workflow which automatically converts and reposits data from the ParaVision structure into the widely supported and openly documented Brain Imaging Data Structure (BIDS). Complementing this workflow we also present operator guidelines for appropriate ParaVision data input, and a programmatic walk-through detailing how preexisting scans with uninterpretable metadata records can easily be made compliant after the acquisition. [ABSTRACT FROM AUTHOR]

Published
2020
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45. Animal Functional Magnetic Resonance Imaging: Trends and Path Toward Standardization.

Author

Mandino, Francesca, Cerri, Domenic H., Garin, Clement M., Straathof, Milou, van Tilborg, Geralda A. F., Chakravarty, M. Mallar, Dhenain, Marc, Dijkhuizen, Rick M., Gozzi, Alessandro, Hess, Andreas, Keilholz, Shella D., Lerch, Jason P., Shih, Yen-Yu Ian, and Grandjean, Joanes

Subjects
FUNCTIONAL magnetic resonance imaging, STANDARDIZATION, ANIMAL communities, ANIMAL populations
Abstract

Animal whole-brain functional magnetic resonance imaging (fMRI) provides a non-invasive window into brain activity. A collection of associated methods aims to replicate observations made in humans and to identify the mechanisms underlying the distributed neuronal activity in the healthy and disordered brain. Animal fMRI studies have developed rapidly over the past years, fueled by the development of resting-state fMRI connectivity and genetically encoded neuromodulatory tools. Yet, comparisons between sites remain hampered by lack of standardization. Recently, we highlighted that mouse resting-state functional connectivity converges across centers, although large discrepancies in sensitivity and specificity remained. Here, we explore past and present trends within the animal fMRI community and highlight critical aspects in study design, data acquisition, and post-processing operations, that may affect the results and influence the comparability between studies. We also suggest practices aimed to promote the adoption of standards within the community and improve between-lab reproducibility. The implementation of standardized animal neuroimaging protocols will facilitate animal population imaging efforts as well as meta-analysis and replication studies, the gold standards in evidence-based science. [ABSTRACT FROM AUTHOR]

Published
2020
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47. List of Contributors

Author

Abdel-Rahman, Emaad M., Ackerman, Hayley D., Akintola, Abimbola, Amdam, Gro V., Atzmon, Gil, Austad, Steve, Awate, Sanket, Balaskó, Márta, Banerjee, Taraswi, Bárcena, Clea, Bartke, Andrzej, Bassi, Ivan, Berendt, Mette, Bijlsma, Maarten F., Bitto, Alessandro, Bizon, Jennifer L., Bollaerts, Ilse, Bonomi, Marco, Borras, Consuelo, Bowman, Brendan T., Brioche, Thomas, Brosh, Robert M., Brown, Richard E., Buck, Kerstin, Burke, Sara N., Buzgariu, Wanda, Cacabelos, Ramón, Camina Martín, M.A., Chaffee, Beth K., Chan, Anthony W.S., Chen, Haolin, Chen, Zhiguo, Cho, In K., Chopard, Angèle, Cogger, Victoria C., Cohen, Alan A., Confino, Rafael, Coppedè, Fabio, Costa, Anthony J., II, Crouch, Jack D., Darcy, Justin, De Groef, Lies, de Mateo Silleras, B., Deepa, Sathyaseelan S., Devau, Gina, Dhenain, Marc, Dills, Chantelle, Duffy, Megan F., Duncan, Francesca E., Dupuis, Gilles, Eaton, Benjamin A., Egan, Josephine M., Ekundayo, Kazadi, Emborg, Marina E., Fischer, D. Luke, Fontes, Pascaline, Fortepiani, Maria Lourdes Alarcon, Fortin, Carl, Franzke, Bernhard, Fülöp, Tamas, Gabriel, Camelia, Galliot, Brigitte, Gambini, Juan, Garneau, Hugo, Gasparini, Laura, Gerhard, Glenn S., Gibson, David C., Gimeno-Mallench, Lucia, Girard, Victor, Greer, Kimberly A., Gribble, Kristin E., Gubbels Bupp, Melanie R., Gudmundsson, Adalsteinn, Hamann, Andrea, Hamblin, Michael R., Harper, James M., Hart, Ronald, Head, Elizabeth, Herd, Heather R., Herrera, Guadalupe, Hisama, Fuki M., Hogan, David B., Holmes, Donna J., Hornsby, Peter J., Howlett, Susan E., Hui, Ka Yi, Jahn, Thomas R., Jávega, Beatriz, Jeffery, William R., Johnson, Sarah A., Jones, Audrey, Jones, Corinne A., Jónsson, Pálmi V., Kane, Alice E., Karasik, David, Kean, Samuel, Keller, Evan T., Keller, Jill M., Kemp, Christopher J., Wong, Ken S.K., Krøll, Jens, Kumar Bharti, Sanjay, Kurkinen, Markku, Larbi, Anis, Lasbleiz, Christelle, Lautier, Corinne, Le Couteur, David G., Le Page, Aurelie, Lin, Hang, López-Otín, Carlos, Lottonen-Raikaslehto, Line, Magden, Elizabeth R., Makrantonaki, Evgenia, Manfredsson, Fredric P., Mark Welch, David B., Marques-Lopes, Jose, Martínez-Romero, Alicia, Mas-Bargues, Cristina, Mayoral, Pablo, Mc Auley, Mark, McQuail, Joseph A., Merentie, Mari, Mestre-Frances, Nadine, Metzger, Jeanette M., Meyer, Keith C., Milner, Teresa A., Mizutani, Claudia M., Monnat, Raymond J., Jr., Mooney, Kathleen, Moons, Lieve, Muck, Joscha, Muniyappa, Ranganath, Nehlin, Jan O., Neubauer, Oliver, Nikolakis, Georgios, Nyman, Jeffry S., O’Connor, José-Enrique, Oshima, Junko, Osiewacz, Heinz D., Papadopoulos, Vassilios, Pavone, Mary Ellen, Pawelec, Graham, Pedersen, Jan T., Perez-Lopez, Gonzalo, Persani, Luca, Pétervári, Erika, Peyman, Azadeh, Plate, Johannes F., Polinski, Nicole K., Py, Guillaume, Quigley, Tyler P., Rae, Eric A., Ram, Jeffrey L., Raubenheimer, David, Reckelhoff, Jane F., Redondo del Río, M.P., Rex-Al Panem Orbon, Jovy, Richardson, Arlan, Ripperger, Jürgen A., Rostás, Ildikó, Rouse, Michael, Rueppell, Olav, Runge, Kurt W., Safdar, Maryam, Sankaran-Walters, Sumathi, Santago, Anthony C., II, Sarvimäki, Anneli, Saul, Katherine R., Schenkelaars, Quentin, Schneider, Brandt L., Schütt, Trine, Shen, He, Shin, Sooyoun, Simpson, Stephen J., Smith, Jessica, Snell, Terry W., Snyder, Jessica M., Solon-Biet, Samantha M., Soós, Szilvia, Sortwell, Caryl E., Sousa-Neves, Rui, Steece-Collier, Kathy, Steins, Anne, Sujkowski, Alyson, Swanberg, Susan E., Teijido, Oscar, Tella, Sri Harsha, Tenk, Judit, Tomczyk, Szymon, Treuting, Piper M., Trouche, Stéphanie G., Tuan, Rocky S., Unnikrishnan, Archana, Valenzano, Dario Riccardo, van Heemst, Diana, Van houcke, Jessie, Van Kempen, Tracey A., van Laarhoven, Hanneke W.M., Verdier, Jean-Michel, Viña, Jose, Wagner, Karl-Heinz, Wahl, Devin, Wenger, Yvan, Wessells, Robert J., Wilcock, Donna M., Witkowski, Jacek M., Wong, Esther, Woodland, Nicole, Yanes Cardozo, Licy L., Ylä-Herttuala, Seppo, Youssef, Sameh A., Yuan, Rong, Zhang, Haitao, Zhou, Zhongjun, Zirkin, Barry R., and Zouboulis, Christos C.

Published
2018
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48. Aβ immunization worsens iron deposits in the choroid plexus and cerebral microbleeds

Author

Joseph-Mathurin, Nelly, Dorieux, Olène, Trouche, Stéphanie G., Boutajangout, Allal, Kraska, Audrey, Fontès, Pascaline, Verdier, Jean-Michel, Sigurdsson, Einar M., Mestre-Francés, Nadine, and Dhenain, Marc

Subjects
Amyloid beta-Peptides, Time Factors, Iron, Polysaccharides, Bacterial, Statistics as Topic, Age Factors, Immunoglobulins, Plaque, Amyloid, Magnetic Resonance Imaging, Article, Peptide Fragments, Disease Models, Animal, Adjuvants, Immunologic, Choroid Plexus, Image Processing, Computer-Assisted, Animals, Immunization, Cheirogaleidae, Cerebral Hemorrhage
Abstract

Anti-amyloid beta (Aβ) immunotherapy provides potential benefits in Alzheimer's disease patients. Nevertheless, strategies based on Aβ1-42 peptide induced encephalomyelitis and possible microhemorrhages. These outcomes were not expected from studies performed in rodents. It is critical to determine if other animal models better predict side effects of immunotherapies. Mouse lemur primates can develop amyloidosis with aging. Here we used old lemurs to study immunotherapy based on Aβ1-42 or Aβ-derivative (K6Aβ1-30). We followed anti-Aβ40 immunoglobulin G and M responses and Aβ levels in plasma. In vivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuroinflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the Aβ1-42 immunogen. This treatment induced immune response and increased Aβ levels in plasma and also microhemorrhages and iron deposits in the choroid plexus. A complementary study of untreated lemurs showed iron accumulation in the choroid plexus with normal aging. Worsening of iron accumulation is thus a potential side effect of Aβ-immunization at prodromal stages of Alzheimer's disease, and should be monitored in clinical trials.

Published
2013

49. In Vivo MRI of Functionalized Iron Oxide Nanoparticles for Brain Inflammation.

Author

Tang, Tang, Valenzuela, Anthony, Petit, Fanny, Chow, Sarah, Leung, Kevin, Gorin, Fredric, Louie, Angelique Y., and Dhenain, Marc

Abstract

Microglia are intrinsic components of the brain immune system and are activated in many central nervous system disorders. The ability to noninvasively image these cells would provide valuable information for both research and clinical applications. Today, most imaging probes for activated microglia are mainly designed for positron emission tomography (PET) and target translocator proteins that also reside on other cerebral cells. The PET images obtained are not specific for microglia-driven inflammation. Here, we describe a potential PET/MRI multimodal imaging probe that selectively targets the scavenger receptor class A (SR-A) expressed on activated microglia. These sulfated dextran-coated iron oxide (SDIO) nanoparticles are avidly taken up by microglia and appear to be nontoxic when administered intravenously in a mouse model. Intravenous administration of this SDIO demonstrated visualization by T2∗-weighted MRI of microglia activated by intracerebral administration of tumor necrosis factor alpha (TNF-α). The contrast was significantly enhanced by SDIO, whereas there was little to no contrast change in animals treated with nontargeted nanoparticles or untreated controls. Thus, SR-A targeting represents a promising strategy to image activated microglia in the brain. [ABSTRACT FROM AUTHOR]

Published
2018
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50. Plasma Amyloid Is Associated with White Matter and Subcortical Alterations and Is Modulated by Age and Seasonal Rhythms in Mouse Lemur Primates.

Author

Gary, Charlotte, Hérard, Anne-Sophie, Hanss, Zoé, and Dhenain, Marc

Subjects
PRIMATE physiology, BLOOD plasma, WHITE matter (Nerve tissue), IMMUNOMODULATORS, LABORATORY mice
Abstract

Accumulation of amyloid-β (Aβ) peptides in the brain is a critical early event in the pathogenesis of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. There is increasing interest in measuring levels of plasma Aβ since this could help in diagnosis of brain pathology. However, the value of plasma Aβ in such a diagnosis is still controversial and factors modulating its levels are still poorly understood. The mouse lemur (Microcebus murinus) is a primate model of cerebral aging which can also present with amyloid plaques and whose Aβ is highly homologous to humans'. In an attempt to characterize this primatemodel and to evaluate the potential of plasma Aβ as a biomarker for brain alterations, we measured plasma Aβ40 concentration in 21 animals aged from 5 to 9.5 years. We observed an age-related increase in plasma Aβ40 levels. We then evaluated the relationships between plasma Aβ40 levels and cerebral atrophy in these mouse lemurs. Voxel-βased analysis of cerebral MR images (adjusted for the age/sex/brain size of the animals), showed that low Aβ40 levels are associated with atrophy of several white matter and subcortical brain regions. These results suggest that low Aβ40 levels in middle-aged/old animals are associated with brain deterioration. One special feature of mouse lemurs is that their metabolic and physiological parameters follow seasonal changes strictly controlled by illumination. We evaluated seasonal-related variations of plasma Aβ40 levels and found a strong effect, with higher plasma A&#94640 concentrations in winter conditions compared to summer. This question of seasonal modulation of Ab plasma levels should be addressed in clinical studies. We also focused on the amplitude of the difference between plasma Ab40 levels during the two seasons and found that this amplitude increases with age. Possible mechanisms leading to these seasonal changes are discussed. [ABSTRACT FROM AUTHOR]

Published
2018
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