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536 results on '"Menon, Vilas"'

3. Neural circuit basis of placebo pain relief

Author

Chen, Chong, Niehaus, Jesse K., Dinc, Fatih, Huang, Karen L., Barnette, Alexander L., Tassou, Adrien, Shuster, S. Andrew, Wang, Lihua, Lemire, Andrew, Menon, Vilas, Ritola, Kimberly, Hantman, Adam W., Zeng, Hongkui, Schnitzer, Mark J., and Scherrer, Grégory

Published
2024
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4. Multi-omic analysis of Huntington’s disease reveals a compensatory astrocyte state

Author

Paryani, Fahad, Kwon, Ji-Sun, Ng, Christopher W., Jakubiak, Kelly, Madden, Nacoya, Ofori, Kenneth, Tang, Alice, Lu, Hong, Xia, Shengnan, Li, Juncheng, Mahajan, Aayushi, Davidson, Shawn M., Basile, Anna O., McHugh, Caitlin, Vonsattel, Jean Paul, Hickman, Richard, Zody, Michael C., Housman, David E., Goldman, James E., Yoo, Andrew S., Menon, Vilas, and Al-Dalahmah, Osama

Published
2024
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8. Cell subtype-specific effects of genetic variation in the Alzheimer’s disease brain

Author

Fujita, Masashi, Gao, Zongmei, Zeng, Lu, McCabe, Cristin, White, Charles C., Ng, Bernard, Green, Gilad Sahar, Rozenblatt-Rosen, Orit, Phillips, Devan, Amir-Zilberstein, Liat, Lee, Hyo, Pearse, II, Richard V., Khan, Atlas, Vardarajan, Badri N., Kiryluk, Krzysztof, Ye, Chun Jimmie, Klein, Hans-Ulrich, Wang, Gao, Regev, Aviv, Habib, Naomi, Schneider, Julie A., Wang, Yanling, Young-Pearse, Tracy, Mostafavi, Sara, Bennett, David A., Menon, Vilas, and De Jager, Philip L.

Published
2024
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9. Xenografted human iPSC-derived neurons with the familial Alzheimer’s disease APPV717I mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator

Author

Qu, Wenhui, Lam, Matti, McInvale, Julie J., Mares, Jason A., Kwon, Sam, Humala, Nelson, Mahajan, Aayushi, Nguyen, Trang, Jakubiak, Kelly A., Mun, Jeong-Yeon, Tedesco, Thomas G., Al-Dalahmah, Osama, Hussaini, Syed A., Sproul, Andrew A., Siegelin, Markus D., De Jager, Philip L., Canoll, Peter, Menon, Vilas, and Hargus, Gunnar

Published
2024
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10. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L, Collins, Ryan L, Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Jerez, Pilar Alvarez, Malik, Laksh, Dawson, Ted M, Rosenthal, Liana S, Albert, Marilyn S, Pletnikova, Olga, Troncoso, Juan C, Masellis, Mario, Keith, Julia, Black, Sandra E, Ferrucci, Luigi, Resnick, Susan M, Tanaka, Toshiko, Soltis, Anthony R, Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, Martinez, Elisa McGrath, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N, Adeleye, Adelani, Wilkerson, Matthew D, Pollard, Harvey B, Dalgard, Clifton L, Gan-Or, Ziv, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian G, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J, Troakes, Claire, Barrett, Matthew J, Beach, Thomas G, Bekris, Lynn M, Bennett, David A, Boeve, Bradley F, Dickson, Dennis W, Faber, Kelley, Ferman, Tanis, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, and Gibbs, J Raphael

Subjects
Biological Sciences, Genetics, Brain Disorders, Dementia, ALS, Rare Diseases, Neurodegenerative, Neurosciences, Human Genome, Frontotemporal Dementia (FTD), Alzheimer's Disease, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Aging, Aetiology, 2.1 Biological and endogenous factors, Neurological, American Genome Center, International LBD Genomics Consortium, International ALS/FTD Consortium, PROSPECT Consortium, Lewy body dementia, amyotrophic lateral sclerosis, case-control study, frontotemporal dementia, genome-wide association study, non–Alzheimer's dementia, resource, structural variant
Abstract

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.

Published
2023

11. NOS1AP is a novel molecular target and critical factor in TDP-43 pathology

Author

Cappelli, Sara, Spalloni, Alida, Feiguin, Fabian, Visani, Giulia, Šušnjar, Urša, Brown, Anna-Leigh, Phatnani, Hemali, Kwan, Justin, Sareen, Dhruv, Broach, James R, Simmons, Zachary, Arcila-Londono, Ximena, Lee, Edward B, Van Deerlin, Vivianna M, Shneider, Neil A, Fraenkel, Ernest, Ostrow, Lyle W, Baas, Frank, Zaitlen, Noah, Berry, James D, Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A, Thompson, Leslie M, Finkbeiner, Steve, Dardiotis, Efthimios, Miller, Timothy M, Chandran, Siddharthan, Pal, Suvankar, Hornstein, Eran, MacGowan, Daniel J, Heiman-Patterson, Terry, Hammell, Molly G, Patsopoulos, Nikolaos A, Butovsky, Oleg, Dubnau, Joshua, Nath, Avindra, Bowser, Robert, Harms, Matt, Aronica, Eleonora, Poss, Mary, Phillips-Cremins, Jennifer, Crary, John, Atassi, Nazem, Lange, Dale J, Adams, Darius J, Stefanis, Leonidas, Gotkine, Marc, Baloh, Robert H, Babu, Suma, Raj, Towfique, Paganoni, Sabrina, Shalem, Ophir, Smith, Colin, Zhang, Bin, Harris, Brent, Broce, Iris, Drory, Vivian, Ravits, John, McMillan, Corey, Menon, Vilas, De Bardi, Marco, Borsellino, Giovanna, Secrier, Maria, Romano, Maurizio, Longone, Patrizia, and Buratti, Emanuele

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Biotechnology, Genetics, Aetiology, 2.1 Biological and endogenous factors, NYGC ALS Consortium, ALS, CAPON/NOS1AP, RNA stability, TDP-43, hnRNPs, Clinical sciences, Biological psychology
Abstract

Many lines of evidence have highlighted the role played by heterogeneous nuclear ribonucleoproteins in amyotrophic lateral sclerosis. In this study, we have aimed to identify transcripts co-regulated by TAR DNA-binding protein 43 kDa and highly conserved heterogeneous nuclear ribonucleoproteins which have been previously shown to regulate TAR DNA-binding protein 43 kDa toxicity (deleted in azoospermia-associated protein 1, heterogeneous nuclear ribonucleoprotein -Q, -D, -K and -U). Using the transcriptome analyses, we have uncovered that Nitric Oxide Synthase 1 Adaptor Protein mRNA is a direct TAR DNA-binding protein 43 kDa target, and in flies, its modulation alone can rescue TAR DNA-binding protein 43 kDa pathology. In primary mouse cortical neurons, we show that TAR DNA-binding protein 43 kDa mediated downregulation of Nitric Oxide Synthase 1 Adaptor Protein expression strongly affects the NMDA-receptor signalling pathway. In human patients, the downregulation of Nitric Oxide Synthase 1 Adaptor Protein mRNA strongly correlates with TAR DNA-binding protein 43 kDa proteinopathy as measured by cryptic Stathmin-2 and Unc-13 homolog A cryptic exon inclusion. Overall, our results demonstrate that Nitric Oxide Synthase 1 Adaptor Protein may represent a novel disease-relevant gene, potentially suitable for the development of new therapeutic strategies.

Published
2022

12. Immune Response following FLASH and Conventional Radiation in Diffuse Midline Glioma

Author

Padilla, Oscar, Minns, Hanna E., Wei, Hong-Jian, Fan, Weijia, Webster-Carrion, Andrea, Tazhibi, Masih, McQuillan, Nicholas M., Zhang, Xu, Gallitto, Matthew, Yeh, Rebecca, Zhang, Zhiguo, Hei, Tom K., Szalontay, Luca, Pavisic, Jovana, Tan, Yuewen, Deoli, Naresh, Garty, Guy, Garvin, James H., Canoll, Peter D., Vanpouille-Box, Claire, Menon, Vilas, Olah, Marta, Rabadan, Raul, Wu, Cheng-Chia, and Gartrell, Robyn D.

Published
2024
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15. INPP5D regulates inflammasome activation in human microglia

Author

Chou, Vicky, Pearse, II, Richard V., Aylward, Aimee J., Ashour, Nancy, Taga, Mariko, Terzioglu, Gizem, Fujita, Masashi, Fancher, Seeley B., Sigalov, Alina, Benoit, Courtney R., Lee, Hyo, Lam, Matti, Seyfried, Nicholas T., Bennett, David A., De Jager, Philip L., Menon, Vilas, and Young-Pearse, Tracy L.

Published
2023
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16. Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states

Author

Al-Dalahmah, Osama, Argenziano, Michael G., Kannan, Adithya, Mahajan, Aayushi, Furnari, Julia, Paryani, Fahad, Boyett, Deborah, Save, Akshay, Humala, Nelson, Khan, Fatima, Li, Juncheng, Lu, Hong, Sun, Yu, Tuddenham, John F., Goldberg, Alexander R., Dovas, Athanassios, Banu, Matei A., Sudhakar, Tejaswi, Bush, Erin, Lassman, Andrew B., McKhann, Guy M., Gill, Brian J. A., Youngerman, Brett, Sisti, Michael B., Bruce, Jeffrey N., Sims, Peter A., Menon, Vilas, and Canoll, Peter

Published
2023
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19. Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

Author

Al-Dalahmah, Osama, Lam, Matti, McInvale, Julie J., Qu, Wenhui, Nguyen, Trang, Mun, Jeong-Yeon, Kwon, Sam, Ifediora, Nkechime, Mahajan, Aayushi, Humala, Nelson, Winters, Tristan, Angeles, Ellen, Jakubiak, Kelly A., Kühn, Rebekka, Kim, Yoon A., De Rosa, Maria Caterina, Doege, Claudia A., Paryani, Fahad, Flowers, Xena, Dovas, Athanassios, Mela, Angeliki, Lu, Hong, DeTure, Michael A., Vonsattel, Jean Paul, Wszolek, Zbigniew K., Dickson, Dennis W., Kuhlmann, Tanja, Zaehres, Holm, Schöler, Hans R., Sproul, Andrew A., Siegelin, Markus D., De Jager, Philip L., Goldman, James E., Menon, Vilas, Canoll, Peter, and Hargus, Gunnar

Published
2024
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20. Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation

Author

Lim, Ryan G, Al-Dalahmah, Osama, Wu, Jie, Gold, Maxwell P, Reidling, Jack C, Tang, Guomei, Adam, Miriam, Dansu, David K, Park, Hye-Jin, Casaccia, Patrizia, Miramontes, Ricardo, Reyes-Ortiz, Andrea M, Lau, Alice, Hickman, Richard A, Khan, Fatima, Paryani, Fahad, Tang, Alice, Ofori, Kenneth, Miyoshi, Emily, Michael, Neethu, McClure, Nicolette, Flowers, Xena E, Vonsattel, Jean Paul, Davidson, Shawn, Menon, Vilas, Swarup, Vivek, Fraenkel, Ernest, Goldman, James E, and Thompson, Leslie M

Subjects
Biological Sciences, Genetics, Rare Diseases, Brain Disorders, Neurodegenerative, Neurosciences, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Huntington's Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Humans, Mice, Biotin, Dietary Supplements, Disease Models, Animal, Huntington Disease, Mice, Transgenic, Nerve Tissue Proteins, Oligodendroglia, Solitary Nucleus, Thiamine
Abstract

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

Published
2022

21. An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Author

Consortium, The NeuroLINCS, Phatnani, Hemali, Kwan, Justin, Sareen, Dhruv, Broach, James R, Simmons, Zachary, Arcila-Londono, Ximena, Lee, Edward B, Van Deerlin, Vivianna M, Shneider, Neil A, Fraenkel, Ernest, Ostrow, Lyle W, Baas, Frank, Zaitlen, Noah, Berry, James D, Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A, Thompson, Leslie M, Finkbeiner, Steve, Dardiotis, Efthimios, Miller, Timothy M, Chandran, Siddharthan, Pal, Suvankar, Hornstein, Eran, MacGowan, Daniel J, Heiman-Patterson, Terry, Hammell, Molly G, Patsopoulos, Nikolaos A, Butovsky, Oleg, Dubnau, Joshua, Nath, Avindra, Bowser, Robert, Harms, Matt, Poss, Mary, Phillips-Cremins, Jennifer, Crary, John, Atassi, Nazem, Lange, Dale J, Adams, Darius J, Stefanis, Leonidas, Gotkine, Marc, Baloh, Robert H, Babu, Suma, Raj, Towfique, Paganoni, Sabrina, Shalem, Ophir, Smith, Colin, Zhang, Bin, Harris, Brent, Broce, Iris, Drory, Vivian, Ravits, John, McMillan, Corey, Menon, Vilas, Wu, Lani, Altschuler, Steven, Li, Jonathan, Lim, Ryan G, Kaye, Julia A, Dardov, Victoria, Coyne, Alyssa N, Wu, Jie, Milani, Pamela, Cheng, Andrew, Thompson, Terri G, Ornelas, Loren, Frank, Aaron, Adam, Miriam, Banuelos, Maria G, Casale, Malcolm, Cox, Veerle, Escalante-Chong, Renan, Daigle, J Gavin, Gomez, Emilda, Hayes, Lindsey, Holewenski, Ronald, Lei, Susan, Lenail, Alex, Lima, Leandro, Mandefro, Berhan, Matlock, Andrea, Panther, Lindsay, Patel-Murray, Natasha Leanna, Pham, Jacqueline, Ramamoorthy, Divya, Sachs, Karen, Shelley, Brandon, Stocksdale, Jennifer, Trost, Hannah, Wilhelm, Mark, Venkatraman, Vidya, Wassie, Brook T, Wyman, Stacia, Yang, Stephanie, Consortium, NYGC ALS, Van Eyk, Jennifer E, Lloyd, Thomas E, and Finkbeiner, Steven

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Neurodegenerative, Clinical Research, ALS, Stem Cell Research, Rare Diseases, Acquired Cognitive Impairment, Stem Cell Research - Induced Pluripotent Stem Cell, Brain Disorders, Neurosciences, Dementia, Stem Cell Research - Induced Pluripotent Stem Cell - Human, 2.1 Biological and endogenous factors, Aetiology, Neurological, Good Health and Well Being, NeuroLINCS Consortium, NYGC ALS Consortium, Biological sciences, Neuroscience, Omics, Systems biology, Systems neuroscience
Abstract

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures.

Published
2021

22. Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer’s disease risk gene SORL1

Author

Lee, Hyo, Aylward, Aimee J., Pearse, Richard V., II, Lish, Alexandra M., Hsieh, Yi-Chen, Augur, Zachary M., Benoit, Courtney R., Chou, Vicky, Knupp, Allison, Pan, Cheryl, Goberdhan, Srilakshmi, Duong, Duc M., Seyfried, Nicholas T., Bennett, David A., Taga, Mariko F., Huynh, Kevin, Arnold, Matthias, Meikle, Peter J., De Jager, Philip L., Menon, Vilas, Young, Jessica E., and Young-Pearse, Tracy L.

Published
2023
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23. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.

Published
2023
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25. A cellular taxonomy of the adult human spinal cord

Author

Yadav, Archana, Matson, Kaya J.E., Li, Li, Hua, Isabelle, Petrescu, Joana, Kang, Kristy, Alkaslasi, Mor R., Lee, Dylan I., Hasan, Saadia, Galuta, Ahmad, Dedek, Annemarie, Ameri, Sara, Parnell, Jessica, Alshardan, Mohammad M., Qumqumji, Feras Abbas, Alhamad, Saud M., Wang, Alick Pingbei, Poulen, Gaetan, Lonjon, Nicolas, Vachiery-Lahaye, Florence, Gaur, Pallavi, Nalls, Mike A., Qi, Yue A., Maric, Dragan, Ward, Michael E., Hildebrand, Michael E., Mery, Pierre-Francois, Bourinet, Emmanuel, Bauchet, Luc, Tsai, Eve C., Phatnani, Hemali, Le Pichon, Claire E., Menon, Vilas, and Levine, Ariel J.

Published
2023
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27. Proteins linking APOE ɛ4 with Alzheimer's disease

Author

Oveisgharan, Shahram, primary, Yu, Lei, additional, de Paiva Lopes, Katia, additional, Tasaki, Shinya, additional, Wang, Yanling, additional, Menon, Vilas, additional, Schneider, Julie A., additional, Seyfried, Nicholas T., additional, and Bennett, David A., additional

Published
2024
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29. FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer’s disease

Author

Lee, Annie J., Raghavan, Neha S., Bhattarai, Prabesh, Siddiqui, Tohid, Sariya, Sanjeev, Reyes-Dumeyer, Dolly, Flowers, Xena E., Cardoso, Sarah A. L., De Jager, Philip L., Bennett, David A., Schneider, Julie A., Menon, Vilas, Wang, Yanling, Lantigua, Rafael A., Medrano, Martin, Rivera, Diones, Jiménez-Velázquez, Ivonne Z., Kukull, Walter A., Brickman, Adam M., Manly, Jennifer J., Tosto, Giuseppe, Kizil, Caghan, Vardarajan, Badri N., and Mayeux, Richard

Published
2022
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30. RNASE6 is a novel modifier of APOE-ε4 effects on cognition

Author

Seto, Mabel, Weiner, Rebecca L., Dumitrescu, Logan, Mahoney, Emily R., Hansen, Shania L., Janve, Vaibhav, Khan, Omair A., Liu, Dandan, Wang, Yanling, Menon, Vilas, De Jager, Philip L., Schneider, Julie A., Bennett, David A., Gifford, Katherine A., Jefferson, Angela L., and Hohman, Timothy J.

Published
2022
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38. A Human Brain Map of Mitochondrial Respiratory Capacity and Diversity

Author

Mosharov, Eugene V., primary, Rosenberg, Ayelet M, additional, Monzel, Anna S, additional, Osto, Corey A., additional, Stiles, Linsey, additional, Rosoklija, Gorazd B., additional, Dwork, Andrew J., additional, Bindra, Snehal, additional, Zhang, Ya, additional, Fujita, Masashi, additional, Mariani, Madeline B, additional, Bakalian, Mihran, additional, Sulzer, David, additional, De Jager, Philip L., additional, Menon, Vilas, additional, Shirihai, Orian S, additional, Mann, J. John, additional, Underwood, Mark, additional, Boldrini, Maura, additional, Thiebaut de Schotten, Michel, additional, and Picard, Martin, additional

Published
2024
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39. An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Author

Phatnani, Hemali, Kwan, Justin, Sareen, Dhruv, Broach, James R., Simmons, Zachary, Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Shneider, Neil A., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos.A., Butovsky, Oleg, Dubnau, Joshua, Nath, Avindra, Bowser, Robert, Harms, Matt, Poss, Mary, Phillips-Cremins, Jennifer, Crary, John, Atassi, Nazem, Lange, Dale J., Adams, Darius J., Stefanis, Leonidas, Gotkine, Marc, Baloh, Robert H., Babu, Suma, Raj, Towfique, Paganoni, Sabrina, Shalem, Ophir, Smith, Colin, Zhang, Bin, Harris, Brent, Broce, Iris, Drory, Vivian, Ravits, John, McMillan, Corey, Menon, Vilas, Wu, Lani, Altschuler, Steven, Li, Jonathan, Lim, Ryan G., Kaye, Julia A., Dardov, Victoria, Coyne, Alyssa N., Wu, Jie, Milani, Pamela, Cheng, Andrew, Thompson, Terri G., Ornelas, Loren, Frank, Aaron, Adam, Miriam, Banuelos, Maria G., Casale, Malcolm, Cox, Veerle, Escalante-Chong, Renan, Daigle, J. Gavin, Gomez, Emilda, Hayes, Lindsey, Holewenski, Ronald, Lei, Susan, Lenail, Alex, Lima, Leandro, Mandefro, Berhan, Matlock, Andrea, Panther, Lindsay, Patel-Murray, Natasha Leanna, Pham, Jacqueline, Ramamoorthy, Divya, Sachs, Karen, Shelley, Brandon, Stocksdale, Jennifer, Trost, Hannah, Wilhelm, Mark, Venkatraman, Vidya, Wassie, Brook T., Wyman, Stacia, Yang, Stephanie, Van Eyk, Jennifer E., Lloyd, Thomas E., Finkbeiner, Steven, Rothstein, Jeffrey D., and Svendsen, Clive N.

Published
2021
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40. Psychosocial experiences are associated with human brain mitochondrial biology.

Author

Trumpff, Caroline, Monzel, Anna S., Sandi, Carmen, Menon, Vilas, Klein, Hans-Ulrich, Fujita, Masashi, Lee, Annie, Petyuk, Vladislav A., Hurst, Cheyenne, Duong, Duc M., Seyfried, Nicholas T., Wingo, Aliza P., Wingo, Thomas S., Yanling Wang, Thambisetty, Madhav, Ferrucci, Luigi, Bennett, David A., De Jager, Philip L., and Picard, Martin

Subjects
HUMAN biology, MITOCHONDRIA, PSYCHOBIOLOGY, BIOLOGY, SIZE of brain
Abstract

Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific associations for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these "mind-mitochondria" associations were masked in bulk RNA-seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self-reported psychosocial experiences are linked to human brain mitochondrial phenotypes. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APPV717I mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.

Author

Qu, Wenhui, Lam, Matti, McInvale, Julie J., Mares, Jason A., Kwon, Sam, Humala, Nelson, Mahajan, Aayushi, Nguyen, Trang, Jakubiak, Kelly A., Mun, Jeong-Yeon, Tedesco, Thomas G., Al-Dalahmah, Osama, Hussaini, Syed A., Sproul, Andrew A., Siegelin, Markus D., De Jager, Philip L., Canoll, Peter, Menon, Vilas, and Hargus, Gunnar

Subjects
ALZHEIMER'S disease, INDUCED pluripotent stem cells, NEURONS, TRANSCRIPTOMES, CELLULAR aging, ROOTSTOCKS
Abstract

Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying the familial AD APPV717I mutation after cell injection into the mouse forebrain. APPV717I mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aβ42 production, elevated phospho-tau, and impaired neurite outgrowth in APPV717I neurons. Two months after transplantation, APPV717I and control neural cells showed robust engraftment but at 12 months post-injection, APPV717I grafts were smaller and demonstrated impaired neurite outgrowth compared to controls, while plaque and tangle pathology were not seen. Single-nucleus RNA-sequencing of micro-dissected grafts, performed 2 months after cell injection, identified significantly altered transcriptome signatures in APPV717I iPSC-derived neurons pointing towards dysregulated synaptic function and axon guidance. Interestingly, APPV717I neurons showed an increased expression of genes, many of which are also upregulated in postmortem neurons of AD patients including the transmembrane protein LINGO2. Downregulation of LINGO2 in cultured APPV717I neurons rescued neurite outgrowth deficits and reversed key AD-associated transcriptional changes related but not limited to synaptic function, apoptosis and cellular senescence. These results provide important insights into transcriptional dysregulation in xenografted APPV717I neurons linked to synaptic function, and they indicate that LINGO2 may represent a potential therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Published
2024
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42. A pharmacological toolkit for human microglia identifies Topoisomerase I inhibitors as immunomodulators for Alzheimer’s disease

Author

Haage, Verena, primary, Tuddenham, John F., additional, Comandante-Lou, Natacha, additional, Bautista, Alex, additional, Monzel, Anna, additional, Chiu, Rebecca, additional, Fujita, Masashi, additional, Garcia, Frankie G., additional, Bhattarai, Prabesh, additional, Patel, Ronak, additional, Buonfiglioli, Alice, additional, Idiarte, Juan, additional, Herman, Mathieu, additional, Rinderspacher, Alison, additional, Mela, Angeliki, additional, Zhao, Wenting, additional, Argenziano, Michael G., additional, Furnari, Julia L., additional, Banu, Matei A., additional, Landry, Donald W., additional, Bruce, Jeffrey N., additional, Canoll, Peter, additional, Zhang, Ya, additional, Nuriel, Tal, additional, Kizil, Caghan, additional, Sproul, Andrew A., additional, de Witte, Lotje D., additional, Sims, Peter A., additional, Menon, Vilas, additional, Picard, Martin, additional, and De Jager, Philip L., additional

Published
2024
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43. Hippocampus Glutathione S Reductase Potentially Confers Genetic Resilience to Cognitive Decline in the of AD-BXD Mouse Population

Author

Saul, Michael C., primary, Litkowski, Elizabeth M., additional, Hadad, Niran, additional, Dunn, Amy R., additional, Boas, Stephanie M., additional, Willcox, Jon A. L., additional, Robbins, Julia E., additional, Wu, Yiyang, additional, Philip, Vivek M., additional, Merrihew, Gennifer E., additional, Park, Jea, additional, De Jager, Philip L., additional, Bridges, Dave E., additional, Menon, Vilas, additional, Bennett, David A., additional, Hohman, Timothy J., additional, MacCoss, Michael J., additional, and Kaczorowski, Catherine C., additional

Published
2024
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44. The spatial landscape of glial pathology and T-cell response in Parkinson’s disease substantia nigra

Author

Jakubiak, Kelly, primary, Paryani, Fahad, additional, Kannan, Adithya, additional, Lee, Jaeseung, additional, Madden, Nacoya, additional, Li, Juncheng, additional, Chen, David, additional, Mahajan, Aayushi, additional, Xia, Shengnan, additional, Flowers, Xena, additional, Menon, Vilas, additional, Sulzer, David, additional, Goldman, James, additional, Sims, Peter A., additional, and Al-Dalahmah, Osama, additional

Published
2024
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46. A Pharmacological Toolkit for Human Microglia Identifies Topoisomerase I Inhibitors as Immunomodulators for Alzheimer's Disease

Author

Haage, Verena Claudia, primary, Tuddenham, John F., additional, Comandante-Lou, Natacha, additional, Bautista, Alex, additional, Monzel, Anna, additional, Chiu, Rebecca, additional, Fujita, Masashi, additional, Garcia, Frankie G., additional, Bhattarai, Prabesh, additional, Patel, Ronak, additional, Buonfiglioli, Alice, additional, Idiarte, Juan, additional, Herman, Mathieu, additional, Rinderspacher, Alison, additional, Mela, Angeliki, additional, Zhao, Wenting, additional, Argenziano, Michael, additional, Furnari, Julia L., additional, Banu, Matei A., additional, Landry, Donald W., additional, Bruce, Jeffrey N., additional, Canoll, Peter, additional, Zhang, Ya, additional, Nuriel, Tal, additional, Kizil, Caghan, additional, Sproul, Andrew, additional, de Witte, Lot D., additional, Sims, Peter A., additional, Menon, Vilas, additional, Picard, Martin, additional, and De Jager, Philip L., additional

Published
2024
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49. Multi‐ethnic genome‐wide, gene‐based study identifies genes that interact with vascular risk factors in Alzheimer’s Disease (AD)

Author

Lee, Annie J, primary, Reyes‐Dumeyer, Dolly, additional, De Jager, Philip L, additional, Bennett, David A. A, additional, Schneider, Julie A, additional, Menon, Vilas, additional, Wang, Yanling, additional, Lantigua, Rafael A., additional, Medrano, Martin, additional, Mejia, Diones Rivera, additional, Jiménez‐Velázquez, Ivonne Z., additional, Kukull, Walter A., additional, Brickman, Adam M., additional, Manly, Jennifer J., additional, Tosto, Giuseppe, additional, Kizil, Caghan, additional, Farrer, Lindsay A., additional, Mez, Jesse B., additional, Chung, Jaeyoon, additional, Vardarajan, Badri N, additional, and Mayeux, Richard, additional

Published
2023
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