Integrated multimodal cell atlas of Alzheimer’s disease
Mariano I. Gabitto(Allen Institute for Brain Science), Kyle J. Travaglini(Allen Institute for Brain Science), Victoria M. Rachleff(Allen Institute for Brain Science), Eitan S Kaplan(Allen Institute for Brain Science), Brian Long(Allen Institute for Brain Science), Jeanelle Ariza(Allen Institute for Brain Science), Yi Ding(Allen Institute for Brain Science), Joseph T. Mahoney(Allen Institute for Brain Science), Nick Dee(Allen Institute for Brain Science), Jeff Goldy(Allen Institute for Brain Science), Erica J. Melief(University of Washington), Anamika Agrawal(University of Washington), Omar Kana(Allen Institute for Brain Science), Xingjian Zhen(Allen Institute for Brain Science), Samuel T. Barlow(Allen Institute for Brain Science), Krissy Brouner(Allen Institute for Brain Science), Jazmin Campos(Allen Institute for Brain Science), John Campos(Allen Institute for Brain Science), Ambrose Carr(Chan Zuckerberg Initiative (United States)), Tamara Casper(Allen Institute for Brain Science), Rushil Chakrabarty(Allen Institute for Brain Science), Michael Clark(Allen Institute for Brain Science), Jonah Cool(Chan Zuckerberg Initiative (United States)), Rachel Dalley(Allen Institute for Brain Science), Martin Darvas(University of Washington), Song‐Lin Ding(Allen Institute for Brain Science), Tim Dolbeare(Allen Institute for Brain Science), Tom Egdorf(Allen Institute for Brain Science), Luke Esposito(Allen Institute for Brain Science), Rebecca Ferrer(Allen Institute for Brain Science), Lynn E. Fleckenstein(Kaiser Permanente Washington Health Research Institute), Rohan Gala(Allen Institute for Brain Science), Amanda Gary(Allen Institute for Brain Science), Emily Gelfand(Allen Institute for Brain Science), Jessica Gloe(Allen Institute for Brain Science), Nathan Guilford(Allen Institute for Brain Science), Junitta Guzman(Allen Institute for Brain Science), Daniel Hirschstein(Allen Institute for Brain Science), Windy Ho(Allen Institute for Brain Science), Madison Hupp(Allen Institute for Brain Science), Tim Jarsky(Allen Institute for Brain Science), Nelson Johansen(Allen Institute for Brain Science), Brian Kalmbach(Allen Institute for Brain Science), Lisa M. Keene(University of Washington), Sarah Khawand(University of Washington), Mitchell D. Kilgore(University of Washington), Amanda Kirkland(University of Washington), Michael Kunst(Allen Institute for Brain Science), Brian R. Lee(Allen Institute for Brain Science), Mckaila Leytze(Allen Institute for Brain Science), Christine L. Mac Donald(University of Washington), Jocelin Malone(Allen Institute for Brain Science), Zoe Maltzer(Allen Institute for Brain Science), Naomi Martin(Allen Institute for Brain Science), Rachel McCue(Allen Institute for Brain Science), Delissa McMillen(Allen Institute for Brain Science), Gonzalo E. Mena(Carnegie Mellon University), Emma Meyerdierks(Allen Institute for Brain Science), Kelly Meyers(Kaiser Permanente Washington Health Research Institute), Tyler Mollenkopf(Allen Institute for Brain Science), Mark Montine(University of Washington), Amber Nolan(University of Washington), Julie Nyhus(Allen Institute for Brain Science), Paul Olsen(Allen Institute for Brain Science), Maiya I Pacleb(University of Washington), Chelsea M. Pagan(Allen Institute for Brain Science), Nicholas Peña(Allen Institute for Brain Science), Trangthanh Pham(Allen Institute for Brain Science), Christina Alice Pom(Allen Institute for Brain Science), Nadia Postupna(University of Washington), Christine Rimorin(Allen Institute for Brain Science), Augustin Ruiz(Allen Institute for Brain Science), Giuseppe-Antonio Saldi(Allen Institute for Brain Science), Aimee Schantz(University of Washington), Nadiya V. Shapovalova(Allen Institute for Brain Science), Staci A. Sorensen(Allen Institute for Brain Science), Brian Staats(Allen Institute for Brain Science), Matt Sullivan(Allen Institute for Brain Science), Susan M. Sunkin(Allen Institute for Brain Science), Carol L. Thompson(Allen Institute for Brain Science), Michael Tieu(Allen Institute for Brain Science), Jonathan T. Ting(Allen Institute for Brain Science), Amy Torkelson(Allen Institute for Brain Science), Tracy Tran(Allen Institute for Brain Science), Nasmil Valera Cuevas(Allen Institute for Brain Science), Sarah Walling-Bell(Allen Institute for Brain Science), Ming-Qiang Wang(Allen Institute for Brain Science), Jack Waters(Allen Institute for Brain Science), Angela Wilson(University of Washington), Ming Xiao(University of Washington), David R. Haynor(University of Washington), Nicole M. Gatto(Kaiser Permanente Washington Health Research Institute), Suman Jayadev(University of Washington), Shoaib Mufti(Allen Institute for Brain Science), Lydia Ng(Allen Institute for Brain Science), Shubhabrata Mukherjee(University of Washington), Paul K. Crane(University of Washington), Caitlin S. Latimer(University of Washington), Boaz P. Levi(Allen Institute for Brain Science), Kimberly A. Smith(Allen Institute for Brain Science), Jennie Close(Allen Institute for Brain Science), Jeremy A. Miller(Allen Institute for Brain Science), Rebecca D. Hodge(Allen Institute for Brain Science), Eric B. Larson(University of Washington), Thomas J. Grabowski(University of Washington), Michael Hawrylycz(Allen Institute for Brain Science), C. Dirk Keene(University of Washington), Ed S. Lein(Allen Institute for Brain Science)
Cited by 240Open Access
Abstract
Abstract 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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