Neuropathological and transcriptomic characteristics of the aged brain
Open accessAbstract
As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer’s disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.
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Many postmortem variables are often not provided and could have significant impacts, such as RNA integrity number (RIN), which has been shown to confound analyses of dementia-related DEGs.
“While most studies report very common postmortem factors (for example, age at death, PMI), many variables are often not provided and could have significant impacts, such as RNA integrity number (RIN), which has been shown to confound analyses of dementia-related DEGs77.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [77]
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References 89 · Cited by 134
- Authors
- Miller, J. A., Guillozet-Bongaarts, A., Gibbons, L. E., Postupna, N., Renz, A., Beller, A. E., Sunkin, S. M., Ng, L., Rose, S. E., Smith, K. A., Szafer, A., Barber, C., Bertagnolli, D., Bickley, K., Brouner, K., Caldejon, S., Chapin, M., Chua, M. L., Coleman, N. M., Cudaback, E., Cuhaciyan, C., Dalley, R. A., Dee, N., Desta, T., Dolbeare, T. A., Dotson, N. I., Fisher, M., Gaudreault, N., Gee, G., Gilbert, T. L., Goldy, J., Griffin, F., Habel, C., Haradon, Z., Hejazinia, N., Hellstern, L. L., Horvath, S., Howard, K., Howard, R., Johal, J., Jorstad, N. L., Josephsen, S. R., Kuan, C. L., Lai, F., Lee, E., Lee, F., Lemon, T., Li, X., Marshall, D. A., Melchor, J., Mukherjee, S., Nyhus, J., Pendergraft, J., Potekhina, L., Rha, E. Y., Rice, S., Rosen, D., Sapru, A., Schantz, A., Shen, E., Sherfield, E., Shi, S., Sodt, A. J., Thatra, N., Tieu, M., Wilson, A. M., Montine, T. J., Larson, E. B., Bernard, A., Crane, P. K., Ellenbogen, R. G., Keene, C. D., & Lein, E.
- Affiliations
- Allen Institute for Brain Science (US)
- University of Washington (US)
- Kaiser Permanente Washington Health Research Institute (US)
- University of California, Los Angeles (US)
- Allen Institute for Brain Science, Seattle, United States
- Corresponding author
- Lein, Ed
- ORCID
- Miller, Jeremy A
- Guillozet-Bongaarts, Angela
- Gibbons, Laura E
- Postupna, Nadia
- Renz, Anne
- Beller, Allison E
- Sunkin, Susan M
- Ng, Lydia
- Smith, Kimberly A
- Szafer, Aaron
- Bertagnolli, Darren
- Brouner, Krissy
- Caldejon, Shiella
- Chapin, Mike
- Cudaback, Eiron
- Dalley, Rachel A
- Dee, Nick
- Desta, Tsega
- Dolbeare, Tim A
- Dotson, Nadezhda I
- Fisher, Michael
- Gilbert, Terri L
- Goldy, Jeff
- Griffin, Fiona
- Hejazinia, Nika
- Horvath, Steve
- Jorstad, Nikolas L
- Lai, Florence
- Lee, Eric
- Lee, Felix
- Marshall, Desiree A
- Mukherjee, Shubhabrata
- Nyhus, Julie
- Pendergraft, Julie
- Potekhina, Lydia
- Schantz, Aimee
- Tieu, Michael
- Wilson, Angela M
- Montine, Thomas J
- Larson, Eric B
- Bernard, Amy
- Crane, Paul K
- Ellenbogen, Richard G
- Keene, C Dirk
- Lein, Ed
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-11-09
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5679757
- OpenAlex
- W2767787249
- Cited by
- 134
- References
- 89
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 15 · 2023: 14 · 2022: 14 · 2021: 21 · 2020: 13 · 2019: 14 · 2018: 11
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (P50AG005136, U01AG006781)
- Nancy and Buster Alvord Endowment
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- brain aging, Alzheimer's disease, dementia, hippocampus, cerebral cortex, neuropathology, transcriptomics, gene co-expression, tau pathology, neuroinflammation, RNA quality, Adult Changes in Thought study, gene expression signatures
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Cerebral Cortex, Dementia, Female, Hippocampus, Humans, Male, Gene Expression Profiling
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