Structural Neuroimaging Genetics Interactions in Alzheimer’s Disease

Abstract

This article investigates late-onset cognitive impairment using neuroimaging and genetics biomarkers for subjects participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Eight hundred and eight ADNI subjects were identified and divided into three groups: those with Alzheimer’s Disease (AD), those with mild cognitive impairment (MCI), and asymptomatic normal control (NC) group. Two hundred of the subjects qualified for AD diagnosis at the baseline; three hundred and eighty-three had MCI; and 225 were included in the NC group. The structural magnetic resonance imaging (MRI) data were parcellated using BrainParser, and the 80 most important neuroimaging biomarkers were extracted using the Global Shape Analysis (GSA) Pipeline workflow. We obtained 80 SNPs using Plink analysis via the Pipeline environment. In the AD cohort, rs2137962 was significantly associated with changes in left and right hippocampi and bilaterally in parahippocampal gyri, and rs1498853, rs288503, and rs288496 were significantly associated with hippocampi bilaterally, the right parahippocampal gyrus, and left inferior temporal gyrus. In the MCI cohort, rs17028008 and rs17027976 were significantly associated with right caudate and right fusiform gyrus, and rs2075650 (TOMM40) was significantly associated with right caudate, rs1334496 and rs4829605 were significantly associated with right inferior temporal gyrus. In the NC cohort, Chromosome 15 [rs734854 (STOML1), rs11072463 (PML), rs4886844 (PML) and rs1052242 (PML)] was significantly associated with the both hippocampi and both insular cortex and rs4899412 (RGS6) was significantly associated with caudate related biomarkers. We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 808 subjects in terms of neuroimaging genetics. These results illustrate some of the neuroimaging-genetics associations between the AD, MCI and NC cohorts.

Alteration of perivascular spaces in early cognitive decline

“…Similar processing to Amyloid PET was performed to measure Tau PET SUVR. ADNI-3 Tau PET includes a broad set of regional MRI preprocessing and brain parcellation T1w preprocessing and parcellation was done using the FreeSurfer (v5.3.0) software package, which is freely available [45], and data processing using the Laboratory of Neuro Imaging (LONI) pipeline system (http://pipeline.loni.usc.edu) [46][47][48][49], similar to [50,51]. Brain volume and white matter mask were derived from the Desikan-Killiany atlas [52].…”

Association between miRNAs expression and cognitive performances of Pediatric Multiple Sclerosis patients: A pilot study

“…Finally, the computational analysis identified several genes that represent the target of most of the significant miRNAs (see Table ). Of interest, some of these genes have been reported implicated in diseases with cognitive impairment, for example, BRI3, RGS6, DIP2A, ZBTB16, BACE2, SIRBP1, IGF2BP2, FCRL5, RTN3, FAM46A, MCF2L, SPI1, and TREM1 in Alzheimer's disease (Abd‐Elrahman, Hamilton, Vasefi, & Ferguson, ; Chung et al, ; Comabella et al, ; Dashinimaev, Artyuhov, Bolshakov, Vorotelyak, & Vasiliev, ; De Jager et al, ; Gaikwad et al, ; Gasparoni et al, ; Matsuda, Matsuda, & D'Adamio, ; Moon et al, ; Replogle et al, ; Schott et al, ; Shi, Ge, He, Hu, & Yan, ); or in clinical conditions characterized by behavioral changes, such as NTNG2 in cognitive abnormalities associated with defective axonal amygdalar projections (Huang et al, ) or bipolar disorders (Egger et al, ), or RAB11FIP5, WARS, and HES6 in depression and other mood disorders (Bacaj, Ahmad, Jurado, Malenka, & Sudhof, ; Glubb, Joyce, & Kennedy, ; Musante et al, ). Furthermore, the experimental ablation of CACNA1H , a gene already associated with the RR course of MS (Sadovnick et al, ), was able to trigger affective disorders including anxiety and hippocampus‐dependent recognition memories (Gangarossa, Laffray, Bourinet, & Valjent, ).…”

Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease

“…Within heart, RGS6 functions as an essential modulator of parasympathetic activation to prevent parasympathetic override and severe bradycardia (Yang et al, 2010). Studies relating RGS6 to human diseases are limited, although literature suggests that RGS6-specific modulation of Ga may be involved in regulating several central nervous system diseases such as alcoholism (Stewart et al, 2015), anxiety and depression (Stewart et al, 2014), Parkinson's disease (Bifsha et al, 2014), Alzheimer's disease (Moon et al, 2015), schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics, 2014), and vision (Chograni et al, 2014). Prolonged exposure to alcohol upregulates RGS6 protein in a brain region known as the ventral tegmental area of wild-type mice.…”