IC‐P‐069: Effects of Kibra Polymorphism on White Matter Integrity: Findings from The Wisconsin Registry for Alzheimer’s Prevention
Year: 2016
Type: article
Study design: Observational Study
Abstract: Genetic variation in the KIBRA gene (rs17070145) has been associated with episodic memory, with T-allele non-carriers exhibiting poorer performance than T-allele carriers. In a recent positron emission tomography study, KIBRA T-allele non-carriers exhibited hypometabolism in brain regions previously shown to be metabolically affected by Alzheimer’s disease (AD). Further, non-carriers have been shown to be at increased risk for late-onset AD. To further investigate the impact of this KIBRA variant on brain structures associated with AD, we utilized diffusion-weighted imaging to determine whether T-allele non-carriers exhibit altered white matter microstructure in a cohort of late-middle-aged, cognitively normal adults. 98 participants (age=62.36±5.96 years) from the Wisconsin Registry for Alzheimer’s Prevention underwent multi-shell diffusion-weighted magnetic resonance imaging. Neurite Orientation Dispersion and Density Imaging was applied to produce the intracellular volume fraction of axons and dendrites, termed the neurite density index (NDI). Analysis of covariance, controlling for age and sex, was used to test for the genetic effect of non-carriers on NDI on a voxel-wise basis in SPM12. Significance was inferred at p<0.001 uncorrected with cluster extent >100 voxels. Compared with T-allele carriers, non-carriers demonstrated decreased NDI in the right precuneal and lateral occipital white matter, the left temporal part of the superior longitudinal fascicle, and bilaterally in the corpus callosum and superior occipito-frontal fascicles. This study provides novel diffusion MRI based evidence of altered white matter integrity in KIBRA T-allele non-carriers in brain areas known to be affected in AD. Specifically, decreased neurite density in the occipito-frontal fascicles and corpus callosum correspond with white matter pathology associated with the progression of AD. Furthermore, the reductions in white matter integrity in the superior longitudinal fascicle and precuneal cerebral white matter pose a possible mechanism underlying the shared metabolic signatures previously demonstrated in AD and KIBRA T-allele non-carriers. Our findings further strengthen KIBRA’s connection to the neurobiological processes involved in memory and susceptibility to AD, and suggest a potential protective role of KIBRA’s T-allele against the pathophysiological processes of AD.
Source: Alzheimer s & Dementia
Authors: Karly Alex Cody, Andrew P. Merluzzi, Jennifer M. Oh, Annie M. Racine, Stephanie A. Schultz, Elizabeth A. Boots, Douglas C. Dean, Hui Zhang, Nagesh Adluru, Catherine L. Gallagher, Cynthia M. Carlsson, Bruce P. Hermann, Howard A. Rowley, Sanjay Asthana, Mark A. Sager, Sterling C. Johnson, Andrew L. Alexander, Barbara B. Bendlin, Ozioma C. Okonkwo
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4230700781