title: VSNL1 Co-Expression Networks in Aging Include Calcium Signaling, Synaptic Plasticity, and Alzheimer's Disease Pathways.
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.
authors: Department of Biostatistics, University of Pittsburgh , Pittsburgh, PA , USA.
authors: Chien-Wei
authors: CW
authors: Lin
authors: Department of Biostatistics, University of Pittsburgh , Pittsburgh, PA , USA.
authors: Lun-Ching
authors: LC
authors: Chang
authors: Department of Biostatistics, University of Pittsburgh , Pittsburgh, PA , USA.
authors: George C
authors: GC
authors: Tseng
authors: Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA , USA.
authors: Caitlin M
authors: CM
authors: Kirkwood
authors: Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA , USA ; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Departments of Psychiatry and Pharmacology & Toxicology, University of Toronto , Toronto, ON , Canada.
authors: Etienne L
authors: EL
authors: Sibille
authors: Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA , USA ; Department of Neurology, University of Pittsburgh , Pittsburgh, PA , USA ; VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System , Pittsburgh, PA , USA.
authors: Robert A
authors: RA
authors: Sweet
keywords: Alzheimer disease; calcium signaling; co-expression networks; synaptic plasticity; visinin-like 1; visinin-like protein 1