• Similarities and differences b...

*Result*: Similarities and differences between Alzheimer's disease and schizophrenia: drug target Mendelian randomization and transcriptome analysis.

Title:
Similarities and differences between Alzheimer's disease and schizophrenia: drug target Mendelian randomization and transcriptome analysis.
Authors:
Zhang Y; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Shao J; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Liang B; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China., He Y; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Wen Z; Xinjiang medical university, Xinjiang, China., Cai B; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Jie L; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Source:
International journal of medical sciences [Int J Med Sci] 2026 Jan 01; Vol. 23 (1), pp. 133-145. Date of Electronic Publication: 2026 Jan 01 (Print Publication: 2026).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101213954 Publication Model: eCollection Cited Medium: Internet ISSN: 1449-1907 (Electronic) Linking ISSN: 14491907 NLM ISO Abbreviation: Int J Med Sci Subsets: MEDLINE
Imprint Name(s):
Original Publication: [Australia] : Ivyspring International Publisher, c2004-
MeSH Terms:
Alzheimer Disease*/genetics , Alzheimer Disease*/drug therapy , Alzheimer Disease*/blood , Schizophrenia*/genetics , Schizophrenia*/drug therapy , Schizophrenia*/blood , Arthritis, Rheumatoid*/genetics , Arthritis, Rheumatoid*/blood, Iceland/epidemiology ; Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Gene Expression Profiling ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Transcriptome ; Linkage Disequilibrium
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Entry Date(s):
Date Created: 20251216 Date Completed: 20251216 Latest Revision: 20260102
Update Code:
20260130
PubMed Central ID:
PMC12702048
DOI:
10.7150/ijms.119636
PMID:
41399369
Database:
MEDLINE

*Further Information*

*Background: Alzheimer's disease (AD) and schizophrenia (SZ) are two complex neuropsychiatric disorders characterized by significant cognitive impairment. The relationship between them is complex and multifaceted. Understanding these similarities and differences is crucial for identifying common therapeutic targets. Methods: Genetic data on plasma proteome were obtained from Icelandic datasets. Genetic variants associated with circulating inflammatory proteins, rheumatoid arthritis (RA) and AD and SZ, were sourced from large GWAS datasets. Mendelian randomization analyses were performed, and transcriptome analysis were applied to confirm the finding. Results: We observed an association between the genetic loci of the AD and SZ traits (p < 0.05) by Linkage Disequilibrium Score Regression. Furthermore, our analysis indicates that RA has a protective effect against AD (OR: 0.36, p = 0.005) while potentially increasing the risk for SZ (OR: 2.49, p = 2.06 × 10⁻⁷). Among the 1,729 proteins analyzed, 16 proteins exhibited significant inverse causal relationships with AD and positive causal relationships with SZ. Notably, DECR2 emerged as a potential therapeutic target, showing opposing effects in AD and SZ as revealed by SMR analysis and colocalization. Conclusions: This study identifies causal proteins linked to AD and SZ, enhancing the understanding of their molecular etiology and supporting targeted therapeutics development.
(© The author(s).)*

*Competing Interests: The authors have declared that no competing interest exists.*