Abstract
Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder currently affecting 45 million people worldwide, ranking as the 6th highest cause of death. Throughout the development and progression of AD, over 90% of patients display behavioral and psychological symptoms of dementia (BPSD), with some of these symptoms occurring before memory deficits and therefore serving as potential early predictors of AD-related cognitive decline. However, the biochemical links between AD and BPSD are not known. In this study, we explored the molecular interactions between AD and BPSD using protein-protein interaction (PPI) networks built from OMIM (Online Mendelian Inheritance in Man) genes that were related to AD and two distinct BPSD domains, the Affective Domain and the Hyperactivity, Impulsivity, Disinhibition, and Aggression (HIDA) Domain. Our results yielded 8 unique proteins for the Affective Domain (RHOA, GRB2, PIK3R1, HSPA4, HSP90AA1, GSK3beta, PRKCZ, and FYN), 5 unique proteins for the HIDA Domain (LRP1, EGFR, YWHAB, SUMO1, and EGR1), and 6 shared proteins between both BPSD domains (APP, UBC, ELAV1, YWHAZ, YWHAE, and SRC) and AD. These proteins might suggest specific targets and pathways that are involved in the pathogenesis of these BPSD domains in AD.
Highlights
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and is the most common form of dementia with over 40 million people affected worldwide[1]
In this study, using the protein-protein interaction (PPI) network analysis approach, we investigated the proteomic links between AD and select behavioral and psychological symptoms of dementia (BPSD) domains, namely the Affective Domain and HIDA Domain
We used publicly available, bioinformatic databases to investigate the possible interactions between AD and the Affective and HIDA Domains and discovered a specific set of shared essential proteins that may be involved in each BPSD domain
Summary
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and is the most common form of dementia with over 40 million people affected worldwide[1]. Some studies[14, 15, 17, 24] have used PPI to discover essential proteins, genes, and associated pathways linked to disease pathogenesis and potential therapies. In this study, using the PPI network analysis approach, we investigated the proteomic links between AD and select BPSD domains, namely the Affective Domain and HIDA Domain. We selected these two BPSD domains as their symptoms are the best studied outside AD pathogenesis. Our study reveals intrinsic protein connections between AD and BPSD
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