1. Integrated multimodal cell atlas of Alzheimer's disease.
- Author
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Gabitto MI, Travaglini KJ, Rachleff VM, Kaplan ES, Long B, Ariza J, Ding Y, Mahoney JT, Dee N, Goldy J, Melief EJ, Agrawal A, Kana O, Zhen X, Barlow ST, Brouner K, Campos J, Campos J, Carr AJ, Casper T, Chakrabarty R, Clark M, Cool J, Dalley R, Darvas M, Ding SL, Dolbeare T, Egdorf T, Esposito L, Ferrer R, Fleckenstein LE, Gala R, Gary A, Gelfand E, Gloe J, Guilford N, Guzman J, Hirschstein D, Ho W, Hupp M, Jarsky T, Johansen N, Kalmbach BE, Keene LM, Khawand S, Kilgore MD, Kirkland A, Kunst M, Lee BR, Leytze M, Mac Donald CL, Malone J, Maltzer Z, Martin N, McCue R, McMillen D, Mena G, Meyerdierks E, Meyers KP, Mollenkopf T, Montine M, Nolan AL, Nyhus JK, Olsen PA, Pacleb M, Pagan CM, Peña N, Pham T, Pom CA, Postupna N, Rimorin C, Ruiz A, Saldi GA, Schantz AM, Shapovalova NV, Sorensen SA, Staats B, Sullivan M, Sunkin SM, Thompson C, Tieu M, Ting JT, Torkelson A, Tran T, Valera Cuevas NJ, Walling-Bell S, Wang MQ, Waters J, Wilson AM, Xiao M, Haynor D, Gatto NM, Jayadev S, Mufti S, Ng L, Mukherjee S, Crane PK, Latimer CS, Levi BP, Smith KA, Close JL, Miller JA, Hodge RD, Larson EB, Grabowski TJ, Hawrylycz M, Keene CD, and Lein ES
- 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., (© 2024. The Author(s).)- Published
- 2024
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