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| Principal Investigator | |
| Principal Investigator's Name: | TAMIL INIYAN GUNASEKARAN |
| Institution: | Chosun University |
| Department: | National Research Center for Dementia |
| Country: | |
| Proposed Analysis: | Title: Ethnic effect on Alzheimer’s disease high-risk genetic loci associated with β-amyloid burden and cortical atrophy Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, which is characterized by memory loss, cognitive decline and dementia [1]. The clinical symptoms in AD appears as a result from the deposition of toxic β-amyloid neuritic plaques and tau neurofibrillary tangles in the brain [2]. β-amyloid plaque deposition in the brain cortex is a neuropathological hallmark of AD and it is thought to begin before the onset of cognitive impairment [3]. In the late onset Alzheimer’s disease, several proposed mechanisms have related the apolipoprotein E (APOE) Ꜫ4 allele to reduced clearance and increased aggregation of β-amyloid plaques in the brain. Though APOE Ꜫ4 is related to β-amyloid burden, the additional contributing factors are still need to be discovered. With the advancements in the radiotracers for the detection of β-amyloid burden, the usage of amyloid PET as endo-phenotypes has become an established method to identify genetic variants associated with AD pathology [4]. The combination of structural Magnetic Resonance Imaging and genetics have also created a better understanding on neurodegenerative process in many diseases including AD [5]. Moreover, a prior study suggests that β-amyloid deposition accelerates brain atrophy in one-third of asymptomatic elderly individuals [6]. Our aim is to identify AD high-risk alleles that are associated with β-amyloid deposition and to investigate its synergistic interaction with cortical atrophy. However, our recently concluded study using APOE genotypes suggest that there is a significant difference in APOE ε4 allele dependent brain atrophy in East Asian compared to Caucasians. With our interesting results on ethnic differences in brain atrophy, it is imperative to conduct genome-wide association study with β-amyloid deposition in Caucasian and East Asian population to investigate the ethnicity effect. Nevertheless, we want to identify the ethnic differences in the synergistic interaction effect of β-amyloid deposition and cortical atrophy by comparing Caucasian and East Asian population. References 1. Liu, M., et al., Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis. Scientific Reports, 2014. 4: p. 4383. 2. Stage, E., et al., The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2016. 5: p. 53-66. 3. Akamatsu, G., et al., Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI. Physics in Medicine & Biology, 2016. 61(15): p. 5768. 4. Ramanan, V.K., et al., GWAS of longitudinal amyloid accumulation on (18)F-florbetapir PET in Alzheimer’s disease implicates microglial activation gene IL1RAP. Brain, 2015. 138(10): p. 3076-3088. 5. Kochunov, P., et al., Genetic Analysis of Cortical Thickness and Fractional Anisotropy of Water Diffusion in the Brain. Frontiers in Neuroscience, 2011. 5(120). 6. Ge, T., et al., Dissociable influences of APOE ε4 and polygenic risk of AD dementia on amyloid and cognition. Neurology, 2018. 90(18): p. e1605-e1612. |
| Additional Investigators |
