Research Project 2 Alzheimer's disease (AD) is the most common cause of dementia, affecfing about 5 million individuals in the US. Small noncoding RNAs, 21 to 30 nucleotides in length, including microRNAs (miRNAs), small interfering RNAs (siRNAs), repeat-associated small interfering RNAs, and piwi-associated RNAs, shape diverse cellular pathways. MiRNAs are sequence specific regulators of posttranscriptlonal gene expression and are believed to regulate the expression of thousands of target mRNAs, with each mRNA targeted by mulfiple miRNAs. Although it has been esfimated that miRNAs could regulate as many as one-third of human genes, highthroughput sequencing data indicate that only a portion of small RNAs in the genome have been discovered so far. Researchers have shown that the expression of RNA is altered in AD brains;however, a role for miRNAs in the pathogenesis of AD has not been established. We have established high-throughput expression profiling of miRNAs and small RNAs in the lab. Using the brain fissues of AD pafients from Emory ADRC Neuropathology Core, we have analyzed the expression of all known miRNAs and identified selective miRNAs are altered specifically in AD. In the proposed study, we plan to test the hypothesis that selective miRNA(s) that are aberrantly expressed in the brain tissues of AD patients modulate the pathogenesis of AD by post-transcriptionally regulating the expression of speciflc mRNAs that are involved in AD. Specifically, we plan to: 1) Identify and validate the altered expression of selective small RNAs in AD brain tissues;2) Identify the mRNA targets of the miRNAs aberrantly expressed in AD brain tissues;and 3) Determine whether the miRNAs aberranfiy expressed in AD brain fissues modulate AD pathogenesis in AD mouse model.
Understanding of the role of small RNAs in AD will not only provide us insight into the molecular pathogenesis of AD, but also potentially provide new targets for further research and therapeutic development.
|Sano, Mary; Zhu, Carolyn W; Grossman, Hillel et al. (2017) Longitudinal Cognitive Profiles in Diabetes: Results From the National Alzheimer's Coordinating Center's Uniform Data. J Am Geriatr Soc 65:2198-2204|
|Devanand, Davangere P; Liu, Xinhua; Brown, Patrick J (2017) Impact of Functional Deficits in Instrumental Activities of Daily Living in Mild Cognitive Impairment: A Clinical Algorithm to Predict Progression to Dementia. Alzheimer Dis Assoc Disord 31:55-61|
|Diner, Ian; Dooyema, Jeromy; Gearing, Marla et al. (2017) Generation of Clickable Pittsburgh Compound B for the Detection and Capture of ?-Amyloid in Alzheimer's Disease Brain. Bioconjug Chem 28:2627-2637|
|LoBue, Christian; Wadsworth, Hannah; Wilmoth, Kristin et al. (2017) Traumatic brain injury history is associated with earlier age of onset of Alzheimer disease. Clin Neuropsychol 31:85-98|
|Tripodis, Yorghos; Alosco, Michael L; Zirogiannis, Nikolaos et al. (2017) The Effect of Traumatic Brain Injury History with Loss of Consciousness on Rate of Cognitive Decline Among Older Adults with Normal Cognition and Alzheimer's Disease Dementia. J Alzheimers Dis 59:251-263|
|Bell, S P; Liu, D; Samuels, L R et al. (2017) Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E ?4 and the Risk of Cognitive Decline and Incident Dementia. J Nutr Health Aging 21:1259-1267|
|Brenowitz, Willa D; Hubbard, Rebecca A; Keene, C Dirk et al. (2017) Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample. Alzheimers Dement 13:654-662|
|Wingo, A P; Almli, L M; Stevens, J S et al. (2017) Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs. Mol Psychiatry 22:774-783|
|Jutkowitz, Eric; Kane, Robert L; Gaugler, Joseph E et al. (2017) Societal and Family Lifetime Cost of Dementia: Implications for Policy. J Am Geriatr Soc 65:2169-2175|
|Moheb, Negar; Mendez, Mario F; Kremen, Sarah A et al. (2017) Executive Dysfunction and Behavioral Symptoms Are Associated with Deficits in Instrumental Activities of Daily Living in Frontotemporal Dementia. Dement Geriatr Cogn Disord 43:89-99|
Showing the most recent 10 out of 373 publications