Late onset Alzheimer disease – the most common form of the degenerative neurological disease – has complicated genetic underpinnings.
Tricia Thornton-Wells, Ph.D., assistant professor of Molecular Physiology and Biophysics, and colleagues explored the association of gene-gene interactions with neuroimaging measurements from participants in the Alzheimer’s Disease Neuroimaging Initiative. They tested the association of specific gene pairs with MRI measurements of the brain’s inferior lateral ventricles (ILV). Increasing ILV volume, which reflects neuronal degeneration in the hippocampus and entorhinal cortex, correlates with Alzheimer disease status and progression.
The investigators identified four genetic interactions associated with changes in the right ILV, and one of the four – the gene-gene pair SYNJ2–PI4KA – was also associated with changes in the left ILV. Both genes belong to the inositol phosphate signaling pathway, suggesting that disruptions in this pathway may reduce neuronal cell survival and lead to increased ventricle volumes.
Functional analyses of the genetic interactions reported in the January issue of the Journal of Alzheimer’s Disease could lead to the identification of new targets for clinical intervention or diagnosis.
The current study was funded in part by grants from the National Institutes of Health (AG036445, GM007347, MH065215). Data collection and sharing for the project was funded by the Alzheimer’s Disease Neuroimaging Initiative (NIH grant AG024904).
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