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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
United States
Zip Code
Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-9
Zhang, Yuhai; Zhou, Xiao-Hua; Meranus, Dana H et al. (2016) Benzodiazepine Use and Cognitive Decline in Elderly With Normal Cognition. Alzheimer Dis Assoc Disord 30:113-7
LeVine 3rd, Harry; Walker, Lary C (2016) What amyloid ligands can tell us about molecular polymorphism and disease. Neurobiol Aging 42:205-12
Holler, Christopher J; Taylor, Georgia; McEachin, Zachary T et al. (2016) Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia. Mol Neurodegener 11:46
Buijsen, R A M; Visser, J A; Kramer, P et al. (2016) Presence of inclusions positive for polyglycine containing protein, FMRpolyG, indicates that repeat-associated non-AUG translation plays a role in fragile X-associated primary ovarian insufficiency. Hum Reprod 31:158-68
Forrester, Sarah N; Gallo, Joseph J; Smith, Gwenn S et al. (2016) Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia. Am J Geriatr Psychiatry 24:117-25
Rui, Yanfang; Zheng, James Q (2016) Amyloid β oligomers elicit mitochondrial transport defects and fragmentation in a time-dependent and pathway-specific manner. Mol Brain 9:79
White, Matthew T; Shaw, Leslie M; Xie, Sharon X et al. (2016) Evaluation of Cerebrospinal Fluid Assay Variability in Alzheimer's Disease. J Alzheimers Dis 51:463-70
Seyfried, Nicholas T; Dammer, Eric B; Swarup, Vivek et al. (2016) A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease. Cell Syst :
Hampstead, B M; Khoshnoodi, M; Yan, W et al. (2016) Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults. Neuroimage 124:997-1008

Showing the most recent 10 out of 293 publications