Alzheimer's disease (AD) presently affects over 5 million Americans and is projected to affect 15 million by 2050. Biomarkers are presently the only feasible approach for diagnosing and quantifying disease-associated changes in the latent AD stage during which a successful disease-modifying therapeutic intervention would realize the greatest impact. High-throughput neuroimaging and genetics have a proven track record for critically advancing our understanding of disease mechanisms and promoting therapeutic development. Our goals are to develop a multimodal biomarker AD risk assessment tool using the prospectively collected imaging, genetic and gene expression ImaGene data set. We propose to apply advanced imaging genetics statistical approaches to achieve the following three aims: 1) identify a discovery set of AD-relevant candidate imaging and genetic biomarkers; 2) select gene expression variables with strong evidence for biological relevance to AD; and 3) develop and validate a multimodal classifier capable of accurately assessing one's risk for future conversion to AD. The discovery of critical disease-related pathways will fundamentally advance our understanding of the molecular and genetic triggers of AD and bring us closer to genomic-based interventions and personalized risk assessment.

Public Health Relevance

The proposed research is relevant to public health as there is an urgent need for biomarkers capable of early and presymptomatic diagnosis and for discovery of critical disease-associated pathways. The proposed research is highly relevant to the mission of NIA because it will 1) identify and test key imaging and peripheral blood genetic biomarkers that when combined will help diagnose early AD and 2) critically inform AD drug development.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Clinical Neuroscience and Neurodegeneration Study Section (CNN)
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Hsiao, John
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Mustafa, Rafid; Brosch, Jared R; Rabinovici, Gil D et al. (2018) Patient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging. Alzheimer Dis Assoc Disord 32:35-42
Cong, Shan; Risacher, Shannon L; West, John D et al. (2018) Volumetric comparison of hippocampal subfields extracted from 4-minute accelerated vs. 8-minute high-resolution T2-weighted 3T MRI scans. Brain Imaging Behav 12:1583-1595
Apostolova, Liana G; Risacher, Shannon L; Duran, Tugce et al. (2018) Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis. JAMA Neurol 75:328-341
Du, Lei; Liu, Kefei; Yao, Xiaohui et al. (2017) Pattern Discovery in Brain Imaging Genetics via SCCA Modeling with a Generic Non-convex Penalty. Sci Rep 7:14052
Wilhalme, Holly; Goukasian, Naira; De Leon, Fransia et al. (2017) A comparison of theoretical and statistically derived indices for predicting cognitive decline. Alzheimers Dement (Amst) 6:171-181
Liu, Kefei; Yao, Xiaohui; Yan, Jingwen et al. (2017) Transcriptome-Guided Imaging Genetic Analysis via a Novel Sparse CCA Algorithm. Graphs Biomed Image Anal Comput Anat Imaging Genet (2017) 10551:220-229
Deters, Kacie D; Nho, Kwangsik; Risacher, Shannon L et al. (2017) Genome-wide association study of language performance in Alzheimer's disease. Brain Lang 172:22-29
Blanken, Anna E; Hurtz, Sona; Zarow, Chris et al. (2017) Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI. Neuroimage Clin 15:56-61
Sokolow, Sophie; Li, Xiaohui; Chen, Lucia et al. (2017) Deleterious Effect of Butyrylcholinesterase K-Variant in Donepezil Treatment of Mild Cognitive Impairment. J Alzheimers Dis 56:229-237
Brosch, Jared R; Farlow, Martin R; Risacher, Shannon L et al. (2017) Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials. Neurotherapeutics 14:62-68

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