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Abstract Details

Proteostasis Network Changes in Dermal Fibroblasts in Aging and Neurodegeneration
Aging, Dementia, and Behavioral Neurology
P2 - Poster Session 2 (11:45 AM-12:45 PM)
3-001
To identify biomarkers of proteostasis dysfunction in fibroblasts in aging and subjects with underlying neurodegenerative disorders. 
Skin demonstrates visible signs of aging as well as aging-associated proteome changes, neurodegenerative phenotypes and proteostasis network alterations. Dysfunctional proteostasis, or protein processing, may be an important mechanism contributing to neurodegenerative disorders. We hypothesized that proteostasis changes in skin may parallel findings in the brain and/or exert cell non-autonomous effects on the brain. 
We compared existing fibroblast and brain microarray datasets with WGCNA for changes in proteostasis networks.  We also performed proteomics and WGCNA on fibroblasts from controls as well as subjects with dominant mutations in progranulin, C9ORF72 or MAPT. 
We identified a strong correlation between proteostasis network expression profiles in skin and brain, particularly the temporal lobe. Several WGCNA modules exhibited age- and disease-associated changes at both the microarray and proteome levels.

These findings suggest that protein changes in skin may be useful as biomarkers of aging and neurodegenerative disorders. The high correlation in expression profiles between skin and temporal lobe may also suggest a common mechanism of aging/degeneration or possible cell non-autonomous connections between the two organs.

Authors/Disclosures
Ashlyn G. Johnson (Emory University)
PRESENTER 		The institution of Ms. Johnson has received research support from BrightFocus Foundation.
No disclosure on file
No disclosure on file
No disclosure on file
Chad Hales, MD, PhD, FAAN The institution of Dr. Hales has received research support from BrightFocus foundation. The institution of Dr. Hales has received research support from NIH. The institution of Dr. Hales has received research support from State of Georgia. Dr. Hales has a non-compensated relationship as a committee member with AAN that is relevant to AAN interests or activities.