Integrated multimodal cell atlas of Alzheimer's disease.

Autor: Gabitto MI; Allen Institute for Brain Science, Seattle, WA, USA.; Department of Statistics, University of Washington, Seattle, WA, USA., Travaglini KJ; Allen Institute for Brain Science, Seattle, WA, USA., Rachleff VM; Allen Institute for Brain Science, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Kaplan ES; Allen Institute for Brain Science, Seattle, WA, USA., Long B; Allen Institute for Brain Science, Seattle, WA, USA., Ariza J; Allen Institute for Brain Science, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Ding Y; Allen Institute for Brain Science, Seattle, WA, USA., Mahoney JT; Allen Institute for Brain Science, Seattle, WA, USA., Dee N; Allen Institute for Brain Science, Seattle, WA, USA., Goldy J; Allen Institute for Brain Science, Seattle, WA, USA., Melief EJ; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Agrawal A; Center for Data-Driven Discovery for Biology, Allen Institute, Seattle, WA, USA.; Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA., Kana O; Allen Institute for Brain Science, Seattle, WA, USA., Zhen X; Allen Institute for Brain Science, Seattle, WA, USA., Barlow ST; Allen Institute for Brain Science, Seattle, WA, USA., Brouner K; Allen Institute for Brain Science, Seattle, WA, USA., Campos J; Allen Institute for Brain Science, Seattle, WA, USA., Campos J; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Carr AJ; Chan Zuckerberg Initiative, Redwood City, CA, USA., Casper T; Allen Institute for Brain Science, Seattle, WA, USA., Chakrabarty R; Allen Institute for Brain Science, Seattle, WA, USA., Clark M; Allen Institute for Brain Science, Seattle, WA, USA., Cool J; Chan Zuckerberg Initiative, Redwood City, CA, USA., Dalley R; Allen Institute for Brain Science, Seattle, WA, USA., Darvas M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Ding SL; Allen Institute for Brain Science, Seattle, WA, USA., Dolbeare T; Allen Institute for Brain Science, Seattle, WA, USA., Egdorf T; Allen Institute for Brain Science, Seattle, WA, USA., Esposito L; Allen Institute for Brain Science, Seattle, WA, USA., Ferrer R; Allen Institute for Brain Science, Seattle, WA, USA., Fleckenstein LE; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA., Gala R; Allen Institute for Brain Science, Seattle, WA, USA., Gary A; Allen Institute for Brain Science, Seattle, WA, USA., Gelfand E; Allen Institute for Brain Science, Seattle, WA, USA., Gloe J; Allen Institute for Brain Science, Seattle, WA, USA., Guilford N; Allen Institute for Brain Science, Seattle, WA, USA., Guzman J; Allen Institute for Brain Science, Seattle, WA, USA., Hirschstein D; Allen Institute for Brain Science, Seattle, WA, USA., Ho W; Allen Institute for Brain Science, Seattle, WA, USA., Hupp M; Allen Institute for Brain Science, Seattle, WA, USA., Jarsky T; Allen Institute for Brain Science, Seattle, WA, USA., Johansen N; Allen Institute for Brain Science, Seattle, WA, USA., Kalmbach BE; Allen Institute for Brain Science, Seattle, WA, USA.; Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA., Keene LM; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Khawand S; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Kilgore MD; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Kirkland A; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Kunst M; Allen Institute for Brain Science, Seattle, WA, USA., Lee BR; Allen Institute for Brain Science, Seattle, WA, USA., Leytze M; Allen Institute for Brain Science, Seattle, WA, USA., Mac Donald CL; Department of Neurological Surgery, University of Washington, Seattle, WA, USA., Malone J; Allen Institute for Brain Science, Seattle, WA, USA., Maltzer Z; Allen Institute for Brain Science, Seattle, WA, USA., Martin N; Allen Institute for Brain Science, Seattle, WA, USA., McCue R; Allen Institute for Brain Science, Seattle, WA, USA., McMillen D; Allen Institute for Brain Science, Seattle, WA, USA., Mena G; Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA, USA., Meyerdierks E; Allen Institute for Brain Science, Seattle, WA, USA., Meyers KP; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA., Mollenkopf T; Allen Institute for Brain Science, Seattle, WA, USA., Montine M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Nolan AL; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Nyhus JK; Allen Institute for Brain Science, Seattle, WA, USA., Olsen PA; Allen Institute for Brain Science, Seattle, WA, USA., Pacleb M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Pagan CM; Allen Institute for Brain Science, Seattle, WA, USA., Peña N; Allen Institute for Brain Science, Seattle, WA, USA., Pham T; Allen Institute for Brain Science, Seattle, WA, USA., Pom CA; Allen Institute for Brain Science, Seattle, WA, USA., Postupna N; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Rimorin C; Allen Institute for Brain Science, Seattle, WA, USA., Ruiz A; Allen Institute for Brain Science, Seattle, WA, USA., Saldi GA; Allen Institute for Brain Science, Seattle, WA, USA., Schantz AM; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Shapovalova NV; Allen Institute for Brain Science, Seattle, WA, USA., Sorensen SA; Allen Institute for Brain Science, Seattle, WA, USA., Staats B; Allen Institute for Brain Science, Seattle, WA, USA., Sullivan M; Allen Institute for Brain Science, Seattle, WA, USA., Sunkin SM; Allen Institute for Brain Science, Seattle, WA, USA., Thompson C; Allen Institute for Brain Science, Seattle, WA, USA., Tieu M; Allen Institute for Brain Science, Seattle, WA, USA., Ting JT; Allen Institute for Brain Science, Seattle, WA, USA., Torkelson A; Allen Institute for Brain Science, Seattle, WA, USA., Tran T; Allen Institute for Brain Science, Seattle, WA, USA., Valera Cuevas NJ; Allen Institute for Brain Science, Seattle, WA, USA., Walling-Bell S; Allen Institute for Brain Science, Seattle, WA, USA., Wang MQ; Allen Institute for Brain Science, Seattle, WA, USA., Waters J; Allen Institute for Brain Science, Seattle, WA, USA., Wilson AM; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Xiao M; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Haynor D; Department of Radiology, University of Washington, Seattle, WA, USA., Gatto NM; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA., Jayadev S; Department of Neurology, University of Washington, Seattle, WA, USA., Mufti S; Allen Institute for Brain Science, Seattle, WA, USA., Ng L; Allen Institute for Brain Science, Seattle, WA, USA., Mukherjee S; Department of Medicine, University of Washington, Seattle, WA, USA., Crane PK; Department of Medicine, University of Washington, Seattle, WA, USA., Latimer CS; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Levi BP; Allen Institute for Brain Science, Seattle, WA, USA., Smith KA; Allen Institute for Brain Science, Seattle, WA, USA., Close JL; Allen Institute for Brain Science, Seattle, WA, USA., Miller JA; Allen Institute for Brain Science, Seattle, WA, USA., Hodge RD; Allen Institute for Brain Science, Seattle, WA, USA., Larson EB; Department of Medicine, University of Washington, Seattle, WA, USA., Grabowski TJ; Department of Radiology, University of Washington, Seattle, WA, USA.; Department of Neurology, University of Washington, Seattle, WA, USA., Hawrylycz M; Allen Institute for Brain Science, Seattle, WA, USA. mikeh@alleninstitute.org., Keene CD; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. cdkeene@uw.edu., Lein ES; Allen Institute for Brain Science, Seattle, WA, USA. edl@alleninstitute.org.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Dec; Vol. 27 (12), pp. 2366-2383. Date of Electronic Publication: 2024 Oct 14.
DOI: 10.1038/s41593-024-01774-5
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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