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Abstract Details

Meta-analysis of Gene Expression in Early-onset Alzheimer’s Disease
Aging, Dementia, Cognitive, and Behavioral Neurology
P6 - Poster Session 6 (12:00 PM-1:00 PM)
10-004
Alzheimer’s Disease (AD) is the most common neurodegenerative dementia. Early-onset presentation before age 65 can be divided into familial AD (FAD) and sporadic early-onset AD (EOAD). Although several genes have been associated with early-onset AD, there is a need to identify better biomarkers in hopes to assist with novel pharmacotherapies. 
Utilize a meta-analysis platform to elucidate pathogenesis of Alzheimer’s Disease.

The Search Tag Analyze Resource for GEO (STARGEO) platform allows for meta-analysis of genomic signatures of disease and tissue. STARGEO was implemented to search The National Center for Biotechnology Information Gene Expression Omnibus (GEO), an open database with more than 2 million genomic samples. 21 samples were analyzed: 7 neurologically healthy controls and 14 AD patients, including 7 EOAD patients and 7 FAD patients genetically determined by a PSEN1 gene mutation. The meta-data was then analyzed using Ingenuity Pathway Analysis.

Based on meta-analysis results, top upstream regulators were CAMP Responsive Element Binding Protein 1 (CREB1), beta-estradiol, and Synuclein Alpha (SNCA). Additionally, neuroinflammation, GABA, and Opioid signaling were identified as the top canonical pathways. Analysis further revealed significant upregulation of the genes TSNAX, BBIP1, and CMC4. 

Overactivation of the gene regulator CREB, also exhibited in FAD mouse brains with mutant presenilin, reveals that the resultant alteration of gene expression in brains of early-onset AD patients could play a role in the disease’s pathogenesis. In mice, overactivation of CREB resulted in a constitutive CaMK pathway, contributing to increased apoptosis and sensitization of cells to Aβ-induced death. The significance of the opioid signaling pathway also suggests that it may contribute to the pathogenesis of AD. Its dysfunction is linked to the degeneration of cholinergic neurons and potentially hyperphosphorylation of tau and neuroinflammation. The top upregulated genes discussed require further investigation to determine if they may be contributing factors to early-onset AD pathogenesis.

Authors/Disclosures
Daniela Lozano, MD (Trinity Health Grand Rapids)
PRESENTER
Dr. Lozano has nothing to disclose.
Leena Raza No disclosure on file
Jihad Aljabban No disclosure on file
Dexter Hadley No disclosure on file