Dataset Information

Transcriptomics of cortical gray matter thickness decline during normal aging.

ABSTRACT:

Introduction

We performed a whole-transcriptome correlation analysis, followed by the pathway enrichment and testing of innate immune response pathway analyses to evaluate the hypothesis that transcriptional activity can predict cortical gray matter thickness (GMT) variability during normal cerebral aging.

Methods

Transcriptome and GMT data were available for 379 individuals (age range=28-85) community-dwelling members of large extended Mexican American families. Collection of transcriptome data preceded that of neuroimaging data by 17 years. Genome-wide gene transcriptome data consisted of 20,413 heritable lymphocytes-based transcripts. GMT measurements were performed from high-resolution (isotropic 800 ?m) T1-weighted MRI. Transcriptome-wide and pathway enrichment analysis was used to classify genes correlated with GMT. Transcripts for sixty genes from seven innate immune pathways were tested as specific predictors of GMT variability.

Results

Transcripts for eight genes (IGFBP3, LRRN3, CRIP2, SCD, IDS, TCF4, GATA3, and HN1) passed the transcriptome-wide significance threshold. Four orthogonal factors extracted from this set predicted 31.9% of the variability in the whole-brain and between 23.4 and 35% of regional GMT measurements. Pathway enrichment analysis identified six functional categories including cellular proliferation, aggregation, differentiation, viral infection, and metabolism. The integrin signaling pathway was significantly (p<10(-6)) enriched with GMT. Finally, three innate immune pathways (complement signaling, toll-receptors and scavenger and immunoglobulins) were significantly associated with GMT.

Conclusion

Expression activity for the genes that regulate cellular proliferation, adhesion, differentiation and inflammation can explain a significant proportion of individual variability in cortical GMT. Our findings suggest that normal cerebral aging is the product of a progressive decline in regenerative capacity and increased neuroinflammation.

SUBMITTER: Kochunov P

PROVIDER: S-EPMC3759649 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Transcriptomics of cortical gray matter thickness decline during normal aging.

Kochunov P P Charlesworth J J Winkler A A Hong L E LE Nichols T E TE Curran J E JE Sprooten E E Jahanshad N N Thompson P M PM Johnson M P MP Kent J W JW Landman B A BA Mitchell B B Cole S A SA Dyer T D TD Moses E K EK Goring H H H HH Almasy L L Duggirala R R Olvera R L RL Glahn D C DC Blangero J J

NeuroImage 20130524

<h4>Introduction</h4>We performed a whole-transcriptome correlation analysis, followed by the pathway enrichment and testing of innate immune response pathway analyses to evaluate the hypothesis that transcriptional activity can predict cortical gray matter thickness (GMT) variability during normal cerebral aging.<h4>Methods</h4>Transcriptome and GMT data were available for 379 individuals (age range=28-85) community-dwelling members of large extended Mexican American families. Collection of tra ...[more]

PMID: 23707588

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Dataset Information

Transcriptomics of cortical gray matter thickness decline during normal aging.

Introduction

Methods

Results

Conclusion

Publications

Transcriptomics of cortical gray matter thickness decline during normal aging.

Similar Datasets

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