TY - JOUR
KW - Alzheimer's disease
KW - Cellular neuroscience
KW - Epigenomics
KW - Gene expression
AU - Mariano I. Gabitto
AU - Kyle J. Travaglini
AU - Victoria M. Rachleff
AU - Eitan S. Kaplan
AU - Brian Long
AU - Jeanelle Ariza
AU - Yi Ding
AU - Joseph T. Mahoney
AU - Nick Dee
AU - Jeff Goldy
AU - Erica J. Melief
AU - Anamika Agrawal
AU - Omar Kana
AU - Xingjian Zhen
AU - Samuel T. Barlow
AU - Krissy Brouner
AU - Jazmin Campos
AU - John Campos
AU - Ambrose J. Carr
AU - Tamara Casper
AU - Rushil Chakrabarty
AU - Michael Clark
AU - Jonah Cool
AU - Rachel Dalley
AU - Martin Darvas
AU - Song-Lin Ding
AU - Tim Dolbeare
AU - Tom Egdorf
AU - Luke Esposito
AU - Rebecca Ferrer
AU - Lynn E. Fleckenstein
AU - Rohan Gala
AU - Amanda Gary
AU - Emily Gelfand
AU - Jessica Gloe
AU - Nathan Guilford
AU - Junitta Guzman
AU - Daniel Hirschstein
AU - Windy Ho
AU - Madison Hupp
AU - Tim Jarsky
AU - Nelson Johansen
AU - Brian E. Kalmbach
AU - Lisa M. Keene
AU - Sarah Khawand
AU - Mitchell D. Kilgore
AU - Amanda Kirkland
AU - Michael Kunst
AU - Brian R. Lee
AU - Mckaila Leytze
AU - Christine L. Mac Donald
AU - Jocelin Malone
AU - Zoe Maltzer
AU - Naomi Martin
AU - Rachel McCue
AU - Delissa McMillen
AU - Gonzalo Mena
AU - Emma Meyerdierks
AU - Kelly P. Meyers
AU - Tyler Mollenkopf
AU - Mark Montine
AU - Amber L. Nolan
AU - Julie K. Nyhus
AU - Paul A. Olsen
AU - Maiya Pacleb
AU - Chelsea M. Pagan
AU - Nicholas Peña
AU - Trangthanh Pham
AU - Christina Alice Pom
AU - Nadia Postupna
AU - Christine Rimorin
AU - Augustin Ruiz
AU - Giuseppe A. Saldi
AU - Aimee M. Schantz
AU - Nadiya V. Shapovalova
AU - Staci A. Sorensen
AU - Brian Staats
AU - Matt Sullivan
AU - Susan M. Sunkin
AU - Carol Thompson
AU - Michael Tieu
AU - Jonathan T. Ting
AU - Amy Torkelson
AU - Tracy Tran
AU - Nasmil J. Valera Cuevas
AU - Sarah Walling-Bell
AU - Ming-Qiang Wang
AU - Jack Waters
AU - Angela M. Wilson
AU - Ming Xiao
AU - David Haynor
AU - Nicole M. Gatto
AU - Suman Jayadev
AU - Shoaib Mufti
AU - Lydia Ng
AU - Shubhabrata Mukherjee
AU - Paul K. Crane
AU - Caitlin S. Latimer
AU - Boaz P. Levi
AU - Kimberly A. Smith
AU - Jennie L. Close
AU - Jeremy A. Miller
AU - Rebecca D. Hodge
AU - Eric B. Larson
AU - Thomas J. Grabowski
AU - Michael Hawrylycz
AU - C. Dirk Keene
AU - Ed S. Lein
AB - 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.
BT - Nature Neuroscience
DA - 2024-12
DO - 10.1038/s41593-024-01774-5
IS - 12
LA - en
N2 - 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.
PY - 2024
SP - 2366
EP - 2383
T2 - Nature Neuroscience
TI - Integrated multimodal cell atlas of Alzheimer’s disease
UR - https://www.nature.com/articles/s41593-024-01774-5
VL - 27
Y2 - 2024-12-30
SN - 1546-1726
ER -