VSNL1 Co-Expression Networks in Aging Include Calcium Signaling, Synaptic Plasticity, and Alzheimer's Disease Pathways.

Chien-Wei Lin,Caitlin M Kirkwood,George C Tseng,Lun-Ching Chang,Robert A Sweet,Etienne L Sibille

doi:10.3389/fpsyt.2015.00030

Abstract

The visinin-like 1 (VSNL1) gene encodes visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD). Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter obtained from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16 to 91, was processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for calcium signaling, AD, long-term potentiation, long-term depression, and trafficking of AMPA receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP) expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

Highlights

Alzheimer disease (AD) is the most prevalent form of dementia in the United States
We evaluated the hypothesis that visinin-like 1 (VSNL1) may contribute to the development of AD by assessing whether VSNL1 demonstrated age-dependent expression and by determining the brain-related biologic co-expression networks in which VSNL1 participates
VSNL1 co-expression networks included AD pathways and pathways implicated in synaptic pathology in AD, including long-term potentiation, longterm depression, and trafficking of AMPA receptors

Summary

Introduction

Alzheimer disease (AD) is the most prevalent form of dementia in the United States. It is characterized clinically by declining memory, progressive loss of cognitive ability, and behavioral changes. The incidence of AD increases rapidly with increasing age [1]. This suggests a role of brain aging in risk for AD, the basis of this age-dependence is not established. The hallmarks of AD are deposition of extracellular amyloid plaques that are predominantly composed of amyloid-β (Aβ) peptide and intracellular neurofibrillary tangles (NFTs) comprised of hyperphosphorylated microtubule-associated protein tau [2, 3]. Other pathologic changes include synapse and neuron loss, and reactive gliosis [4]

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