The short term objectives of this K02 proposal are: 1) to expand the scope the applicant's active imaging genetic R01 by adding a high-throughput genome-wide epigenetic component;2) to actively seek additional training in the areas of statistical genetics and epigenetics;and 3) to establish new and enhance existing collaborations with prominent statistical and imaging genetics experts. The long-term objective of the K02 award is to bolster the applicant's scientific career and to further facilitate her growth into a prolific and highly successful independent investigator in the AD field. The applicant has developed an active research program focused on the imaging genetic biomarkers of AD. Her recently funded R01 award studies the associations between clinical, imaging and transcriptomic disease-associated traits in a prospective longitudinal cohort of cognitively normal and prodromal AD subjects. The objective of the science integral to this proposal is to expand the scope of the experiments to include newly acquired epigenetic data. The short-term scientific goals are to integrate epigenetics with the genomic, transcriptomic, clinical and imaging data from the parent R01 in order to elucidate the epigenetic effects on gene expression, brain atrophy, brain amyloidosis and disease risk. The long-term scientific goals of the R01 and K02 are to identify novel disease-associated pathways and therapeutic targets. To ensure the success of the proposed work, the applicant will be supported by a diverse group of distinguished collaborators with expertise in highly relevant fields and methods.
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.
|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|
|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|
|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|
|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|
|Ramirez, Leslie M; Goukasian, Naira; Porat, Shai et al. (2016) Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy. Neurobiol Aging 39:82-9|
|Clark, David Glenn; McLaughlin, Paula M; Woo, Ellen et al. (2016) Novel verbal fluency scores and structural brain imaging for prediction of cognitive outcome in mild cognitive impairment. Alzheimers Dement (Amst) 2:113-22|
|Apostolova, Liana G (2016) Alzheimer Disease. Continuum (Minneap Minn) 22:419-34|
Showing the most recent 10 out of 14 publications