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Todd E. Golde, 1275 Center Drive, Gainesville, Florida 32610, USA. Phone: 352.273.9456; Email: tgolde@ufl.edu

Nilüfer Ertekin-Taner: 4500 San Pablo Rd. S #378, Jacksonville, Florida 32224, USA. Phone: 904.953.7103; Email: taner.nilufer@mayo.edu

TEG, NET, and MA conceived the idea. XW, MA, JSR, YM, and SRO performed quality control and analyses. NET, TEG, MA, CF, and NDP developed the study concept. TEG, XW, and NET wrote the manuscript. DWD provided tissue from the Mayo Clinic Brain Bank and neuropathologically characterized the Mayo brain samples. NTS and AIL generated the proteomics data. TN, KGM, MA, and MMC performed sample selection and library preparation. OI, FQTN, and CCGH performed qPCR experiments. MCC and MEM performed immunohistochemistry experiments. TEG, NET, SGY, and YWA supervised the analytical aspects of the project. NET and TEG provided funding, supervision, and direction for the whole study. All authors read and approved the final manuscript.

We are grateful for the participation of the patients and their families, without whom these studies would not have been possible. The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). The Mayo RNA-Seq study was led by Nilüfer Ertekin-Taner (Mayo Clinic, Jacksonville, Florida, as part of the multi-PI (MPI) U01 AG046139 (MPIs Golde, Ertekin-Taner, Younkin, and Price). Samples were obtained from the Mayo Clinic Brain Bank. Data collection was supported through funding from the National Institute on Aging (NIA), NIH (P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, and R01 AG003949); the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01 NS080820); the CurePSP Foundation; and the Mayo Foundation. Study data included samples collected through the Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona, USA. The Brain and Body Donation Program is supported by the NINDS (U24 NS072026, National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders); the NIA (P30 AG19610, Arizona Alzheimer’s Disease Core Center); the Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Research Center); the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001, to the Arizona Parkinson’s Disease Consortium); and the Michael J. Fox Foundation for Parkinson’s Research.

The authors have declared that no conflict of interest exists.

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Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • NETWORKS

Alzheimer's disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions

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Journal Title:

JOURNAL OF CLINICAL INVESTIGATION

Volume:

Volume 132, Number 2

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Article | Final Publisher PDF

Abstract:

Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer’s disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples from patients with AD and progressive supranuclear palsy (PSP), a tauopathy, we identified a striking correlation in the directionality and magnitude of gene expression changes between these 2 neurodegenerative proteinopathies. Further, the transcriptomic changes in AD and PSP brains ware highly conserved between the temporal and cerebellar cortices, indicating that highly similar transcriptional changes occur in pathologically affected and grossly less affected, albeit functionally connected, areas of the brain. Shared up- or downregulated genes in AD and PSP are enriched in biological pathways. Many of these genes also have concordant protein changes and evidence of epigenetic control. These conserved transcriptomic alterations of 2 distinct proteinopathies in brain regions with and without significant gross neuropathology have broad implications. AD and other neurodegenerative diseases are likely characterized by common disease or compensatory pathways with widespread perturbations in the whole brain. These findings can be leveraged to develop multifaceted therapies and biomarkers that address these common, complex, and ubiquitous molecular alterations in neurodegenerative diseases.

Copyright information:

© 2022 Wang et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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