| Autor: |
Mariano Gabitto, Kyle Travaglini, Jeannelle Ariza, Eitan Kaplan, Brian Long, Victoria Rachleff, Yi Ding, Joseph Mahoney, Nick Dee, Jeff Goldy, Erica Melief, Krissy Brouner, Jazmin Compos, John Campos, Ambrose Carr, Tamara Casper, Rushil Chakrabarty, Michael Clark, Jonah Cool, Rachel Dalley, Martin Darvas, Tim Dolbeare, Song-Lin Ding, Tom Egdorf, Luke Esposito, Rebecca Ferrer, Rohan Gala, Amanda Gary, Jessica Gloe, Nathan Guilford, Junitta Guzman, Windy Ho, Tim Jarsky, Nelson Johansen, Brian Kalmbach, Lisa Keene, Sarah Khawand, Mitchell Kilgore, Amanda Kirkland, Michael Kunst, Brian Lee, Christine Mac Donald, Jocelin Malone, Zoe Maltzer, Naomi Martin, Rachel McCue, Delissa McMillen, Emma Meyerdierks, Kelly Meyers, Tyler Mollenkopf, Mark Montine, Amber Nolan, Julie Nyhus, Paul Olsen, Maiya Pacleb, Trangthanh Pham, Christina Pom, Nadia Postupna, Augustin Ruiz, Aimee Schantz, Staci Sorensen, Brian Staats, Matt Sullivan, Susan Sunkin, Carol Thompson, Michael Tieu, Jonathan Ting, Amy Torkelson, Tracy Tran, Nasmil Valera Cuevas, Ming-Qiang Wang, Jack Waters, Angela Wilson, David Haynor, Nicole Gatto, Suman Jayadev, Shoaib Mufti, Lydia Ng, Shubhabrata Mukherjee, Paul Crane, Caitlin Latimer, Boaz Levi, Kimberly Smith, Jennie Close, Jeremy Miller, Rebecca Hodge, Eric Larson, Thomas Grabowski, Michael Hawrylycz, C. Keene, Ed Lein |
| Rok vydání: |
2023 |
| Popis: |
Alzheimer’s disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses the BRAIN Initiative Cell Census Network experimental practices, combining quantitative neuropathology with single cell genomics and spatial transcriptomics, to understand the impact of disease progression on middle temporal gyrus cell types. We used quantitative neuropathology to place 84 cases spanning the spectrum of AD pathology along a continuous disease pseudoprogression score. We used multiomic technologies to profile single nuclei from each donor, mapping their identity to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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