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1. Neuropathological and transcriptomic characteristics of the aged brain

Author

Jeremy A Miller, Angela Guillozet-Bongaarts, Laura E Gibbons, Nadia Postupna, Anne Renz, Allison E Beller, Susan M Sunkin, Lydia Ng, Shannon E Rose, Kimberly A Smith, Aaron Szafer, Chris Barber, Darren Bertagnolli, Kristopher Bickley, Krissy Brouner, Shiella Caldejon, Mike Chapin, Mindy L Chua, Natalie M Coleman, Eiron Cudaback, Christine Cuhaciyan, Rachel A Dalley, Nick Dee, Tsega Desta, Tim A Dolbeare, Nadezhda I Dotson, Michael Fisher, Nathalie Gaudreault, Garrett Gee, Terri L Gilbert, Jeff Goldy, Fiona Griffin, Caroline Habel, Zeb Haradon, Nika Hejazinia, Leanne L Hellstern, Steve Horvath, Kim Howard, Robert Howard, Justin Johal, Nikolas L Jorstad, Samuel R Josephsen, Chihchau L Kuan, Florence Lai, Eric Lee, Felix Lee, Tracy Lemon, Xianwu Li, Desiree A Marshall, Jose Melchor, Shubhabrata Mukherjee, Julie Nyhus, Julie Pendergraft, Lydia Potekhina, Elizabeth Y Rha, Samantha Rice, David Rosen, Abharika Sapru, Aimee Schantz, Elaine Shen, Emily Sherfield, Shu Shi, Andy J Sodt, Nivretta Thatra, Michael Tieu, Angela M Wilson, Thomas J Montine, Eric B Larson, Amy Bernard, Paul K Crane, Richard G Ellenbogen, C Dirk Keene, and Ed Lein

Subjects
Alzheimer's disease, aging, dementia, gene expression, Medicine, Science, Biology (General), QH301-705.5
Abstract

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.

Published
2017
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2. Neuropathological and transcriptomic characteristics of the aged brain

Author

Terri L. Gilbert, Thomas J. Montine, Aaron Szafer, Eiron Cudaback, Nick Dee, Christine Cuhaciyan, Xianwu Li, Kimberly A. Smith, Samuel R Josephsen, Tim A. Dolbeare, Paul K. Crane, Amy Bernard, Nadezhda Dotson, Michael Tieu, Fiona Griffin, Shannon E. Rose, Ed S. Lein, Jeff Goldy, Laura E. Gibbons, Julie Pendergraft, Felix Lee, Nivretta Thatra, Elaine Shen, Elizabeth Rha, Susan M. Sunkin, Garrett Gee, Lydia Potekhina, Nadia Postupna, Darren Bertagnolli, Andy J. Sodt, Nikolas L. Jorstad, Angela L. Guillozet-Bongaarts, Samantha Rice, Jeremy A. Miller, Natalie M Coleman, Zeb Haradon, Tsega Desta, David Rosen, Angela M. Wilson, Justin Johal, Shubhabrata Mukherjee, Kristopher Bickley, Anne Renz, Abharika Sapru, Robert Howard, Desiree A. Marshall, Tracy Lemon, Nika Hejazinia, Rachel A. Dalley, Shu Shi, Steve Horvath, Mindy L Chua, Aimee Schantz, Eric B. Larson, Allison Beller, Michael S. Fisher, Julie Nyhus, C. Dirk Keene, Lydia Ng, Kim Howard, Caroline Habel, Nathalie Gaudreault, Krissy Brouner, Leanne L Hellstern, Shiella Caldejon, Jose Melchor, Emily Sherfield, Chihchau L. Kuan, Mike Chapin, Richard G. Ellenbogen, Chris Barber, Florence Lai, and Eric Lee

Subjects
0301 basic medicine, Male, Amyloid beta, QH301-705.5, Science, Hippocampus, Disease, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Dementia, Humans, Biology (General), Gene, Pathological, Aged, Aged, 80 and over, Cerebral Cortex, General Immunology and Microbiology, biology, business.industry, General Neuroscience, Gene Expression Profiling, aging, Cognition, General Medicine, Alzheimer's disease, medicine.disease, 3. Good health, Tools and Resources, 030104 developmental biology, biology.protein, gene expression, Medicine, Female, business, Neuroscience, 030217 neurology & neurosurgery, Human, dementia
Abstract

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.

Published
2017

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