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.