Brain morphology mediating the effect of genetic risk variants on Alzheimers disease
Breddels, E. M.; Snihirova, Y.; Pishva, E.; Guloksuz, S.; Blokland, G. A. M.; Luykx, J.; Andreassen, O. A.; Linden, D.; van der Meer, D.
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INTRODUCTIONLate-onset Alzheimers disease (LOAD) has been associated with alterations in the morphology of multiple brain structures and it is likely that disease mechanisms differ between brain regions. Coupling genetic determinants of LOAD with measures of brain morphology could localize and identify primary causal neurobiological pathways. METHODSMediation and Mendelian randomization (MR) analysis were performed using common genetic variation, T1 MRI and clinical data collected by UK Biobank and Alzheimers Disease Neuroimaging Initiative. RESULTSThickness of the entorhinal cortex and the volumes of the hippocampus, amygdala, choroid plexus and inferior lateral ventricle mediated the effect of APOE {varepsilon}4 on LOAD. MR showed that a thinner entorhinal cortex, a smaller hippocampus and amygdala, and a larger volume of the choroid plexus and inferior lateral ventricles, increased the risk of LOAD as well as vice versa. DISCUSSIONCombining neuroimaging and genetic data can give insight into the causal neuropathological pathways of LOAD.
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