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Cited by 28Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchBioinformatics and Genomic Networks

Protein-protein interactions underlying the behavioral and psychological symptoms of dementia (BPSD) and Alzheimer’s disease

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Mao, Yimin, Fisher, Daniel W., Yang, Shuxing, Keszycki, Rachel M., Dong, Hongxin·2020·PLOS ONE
DOI 10.1371/journal.pone.0226021PMC PMC6968845
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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.

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  • Integration with protein-protein interaction (PPI) networks has refined AD models by connecting transcriptomic and proteomic layers, particularly when combined with tissue-specific data or prior biological knowledge.

    “Integration with protein–protein interaction (PPI) networks has further refined AD models by connecting transcriptomic and proteomic layers, particularly when combined with tissue-specific data or prior biological knowledge303, 304, 305.”

    From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [303]

    The Introduction and Materials and methods (page numbers unavailable) describe using prior gene information and PPI networks to investigate protein links involving AD. They do not describe integrating transcriptomic and proteomic datasets or combining the study’s network with tissue-specific data; the Introduction mentions brain-region-specific findings from other studies. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Mao, Y., Fisher, D. W., Yang, S., Keszycki, R. M., & Dong, H.
Affiliations
  • Jiangxi University of Science and Technology (CN)
  • Northwestern University (US)
Corresponding author
Dong, Hongxin
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2020-01-17
Volume
15
Issue
1
Pages
e0226021
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0226021
PMC
PMC6968845
OpenAlex
W2999348766
Cited by
28
References
18
Citations by year
2026: 2 · 2025: 11 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 3
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institute of Mental Health (R01MH109466, F30MH10924)
  • National Institute of Aging (R01AG062249)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
Alzheimer's disease, behavioral and psychological symptoms of dementia, protein-protein interaction network, affective symptoms, RhoA, GSK3β, PIK3R1, HSP90AA1, LRP1, EGFR, YWHAB, SUMO1, EGR1, APP, Src kinase
MeSH terms
Affect, Aggression, Alzheimer Disease, Behavior, Humans, Impulsive Behavior, Protein Interaction Maps

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