Integrating Gene and Protein Expression Reveals Perturbed Functional Networks in Alzheimer's Disease.

Cell Rep 2019 07;28(4):1103-1116.e4

Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. Electronic address:

Asymptomatic and symptomatic Alzheimer's disease (AD) subjects may present with equivalent neuropathological burdens but have significantly different antemortem cognitive decline rates. Using the transcriptome as a proxy for functional state, we selected 414 expression profiles of symptomatic AD subjects and age-matched non-demented controls from a community-based neuropathological study. By combining brain tissue-specific protein interactomes with gene networks, we identified functionally distinct composite clusters of genes that reveal extensive changes in expression levels in AD. Global expression for clusters broadly corresponding to synaptic transmission, metabolism, cell cycle, survival, and immune response were downregulated, while the upregulated cluster included largely uncharacterized processes. We propose that loss of EGR3 regulation mediates synaptic deficits by targeting the synaptic vesicle cycle. Our results highlight the utility of integrating protein interactions with gene perturbations to generate a comprehensive framework for characterizing alterations in the molecular network as applied to AD.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2019.06.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503200PMC
July 2019
2 Reads

Publication Analysis

Top Keywords

alzheimer's disease
8
protein interactomes
4
interactomes gene
4
highlight utility
4
gene networks
4
tissue-specific protein
4
brain tissue-specific
4
networks identified
4
functionally distinct
4
vesicle cycle
4
immune response
4
identified functionally
4
cycle highlight
4
utility integrating
4
combining brain
4
non-demented controls
4
interactions gene
4
response downregulated
4
egr3 regulation
4
gene perturbations
4

Similar Publications