Integrated multimodal cell atlas of Alzheimer?s disease
Nature Neuroscience·2024225 cites
20242026
225
Gabitto, Mariano I. and Travaglini, Kyle J. and Rachleff, Victoria M. and Kaplan, Eitan S. and Long, Brian and Ariza, Jeanelle and Ding, Yi and Mahoney, Joseph T. and Dee, Nick and Goldy, Jeff and Melief, Erica J. and Agrawal, Anamika and Kana, Omar and Zhen, Xingjian and Barlow, Samuel T. and Brouner, Krissy and Campos, Jazmin and Campos, John and Carr, Ambrose J. and Casper, Tamara and Chakrabarty, Rushil and Clark, Michael and Cool, Jonah and Dalley, Rachel and Darvas, Martin and Ding, Song-Lin and Dolbeare, Tim and Egdorf, Tom and Esposito, Luke and Ferrer, Rebecca and Fleckenstein, Lynn E. and Gala, Rohan and Gary, Amanda and Gelfand, Emily and Gloe, Jessica and Guilford, Nathan and Guzman, Junitta and Hirschstein, Daniel and Ho, Windy and Hupp, Madison and Jarsky, Tim and Johansen, Nelson and Kalmbach, Brian E. and Keene, Lisa M. and Khawand, Sarah and Kilgore, Mitchell D. and Kirkland, Amanda and Kunst, Michael and Lee, Brian R. and Leytze, Mckaila and Mac Donald, Christine L. and Malone, Jocelin and Maltzer, Zoe and Martin, Naomi and McCue, Rachel and McMillen, Delissa and Mena, Gonzalo and Meyerdierks, Emma and Meyers, Kelly P. and Mollenkopf, Tyler and Montine, Mark and Nolan, Amber L. and Nyhus, Julie K. and Olsen, Paul A. and Pacleb, Maiya and Pagan, Chelsea M. and Pe\~{n}a, Nicholas and Pham, Trangthanh and Pom, Christina Alice and Postupna, Nadia and Rimorin, Christine and Ruiz, Augustin and Saldi, Giuseppe A. and Schantz, Aimee M. and Shapovalova, Nadiya V. and Sorensen, Staci A. and Staats, Brian and Sullivan, Matt and Sunkin, Susan M. and Thompson, Carol and Tieu, Michael and Ting, Jonathan T. and Torkelson, Amy and Tran, Tracy and Valera Cuevas, Nasmil J. and Walling-Bell, Sarah and Wang, Ming-Qiang and Waters, Jack and Wilson, Angela M. and Xiao, Ming and Haynor, David and Gatto, Nicole M. and Jayadev, Suman and Mufti, Shoaib and Ng, Lydia and Mukherjee, Shubhabrata and Crane, Paul K. and Latimer, Caitlin S. and Levi, Boaz P. and Smith, Kimberly A. and Close, Jennie L. and Miller, Jeremy A. and Hodge, Rebecca D. and Larson, Eric B. and Grabowski, Thomas J. and Hawrylycz, Michael and Keene, C. Dirk and Lein, Ed S.
Alzheimer’s disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin+ inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb+ and Vip+ inhibitory neuron subtypes. These findings were replicated in other major AD studies.
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