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Elife. 2017 Nov 9;6. pii: e31126. doi: 10.7554/eLife.31126.

Neuropathological and transcriptomic characteristics of the aged brain.

Author information

1
Allen Institute for Brain Science, Seattle, United States.
2
Department of Medicine, University of Washington, Seattle, United States.
3
Department of Pathology, University of Washington, Seattle, United States.
4
Kaiser Permanente Washington Health Research Institute, Seattle, United States.
5
Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States.
6
Department of Neurological Surgery, University of Washington, Seattle, United States.

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.

KEYWORDS:

Alzheimer's disease; aging; dementia; gene expression; human; neuroscience

PMID:
29120328
PMCID:
PMC5679757
DOI:
10.7554/eLife.31126
[Indexed for MEDLINE]
Free PMC Article

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