• Peripheral blood transcriptome...

Treffer: Peripheral blood transcriptome signatures indicate environmental influences in monozygotic twins discordant for Alzheimer's disease.

Title:
Peripheral blood transcriptome signatures indicate environmental influences in monozygotic twins discordant for Alzheimer's disease.
Authors:
Roh JH; Department of Biomedical Sciences and Department of Physiology, Korea University College of Medicine, Seoul, 02841, South Korea; Department of Neurology, Anam Hospital, Korea University College of Medicine, Seoul, 02841, South Korea., Park C; Laboratory for Brain Gene Regulation and Epigenetics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, South Korea., Kim S; Laboratory for Brain Gene Regulation and Epigenetics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, South Korea., Shin JY; Genome Medicine Institute and Department of Biochemistry, Seoul National University College of Medicine, Seoul, 03080, South Korea., Kim JI; Genome Medicine Institute and Department of Biochemistry, Seoul National University College of Medicine, Seoul, 03080, South Korea., Yoon YW; Department of Biomedical Sciences and Department of Physiology, Korea University College of Medicine, Seoul, 02841, South Korea., Park KW; Department of Neurology, Anam Hospital, Korea University College of Medicine, Seoul, 02841, South Korea., Stein TD; Boston University Alzheimer's Disease Research Center and Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, 02118, USA; VA Boston Healthcare System, Boston, MA, 02130, USA., Lee J; Boston University Alzheimer's Disease Research Center and Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, 02118, USA; VA Boston Healthcare System, Boston, MA, 02130, USA., Lee JH; Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea. Electronic address: jhlee@amc.seoul.kr., Ryu H; Laboratory for Brain Gene Regulation and Epigenetics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, South Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: hoonryu@kist.re.kr.
Source:
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2026 Feb; Vol. 1872 (2), pp. 168073. Date of Electronic Publication: 2025 Oct 14.
Publication Type:
Journal Article; Twin Study
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE
Imprint Name(s):
Original Publication: Amsterdam : Elsevier
MeSH Terms:
Alzheimer Disease*/genetics , Alzheimer Disease*/blood , Alzheimer Disease*/pathology , Twins, Monozygotic*/genetics , Transcriptome*/genetics, Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Brain/metabolism ; Brain/pathology ; Gene Expression Profiling ; Middle Aged
Contributed Indexing:
Keywords: Alzheimer's disease (AD); Environmental factors; Monozygote (MZ) twins; Whole transcriptome sequencing
Entry Date(s):
Date Created: 20251016 Date Completed: 20251116 Latest Revision: 20251203
Update Code:
20260130
DOI:
10.1016/j.bbadis.2025.168073
PMID:
41101396
Database:
MEDLINE

Weitere Informationen

Environmental factors have been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). Because monozygotic (MZ) twins share identical genetic backgrounds, they provide a unique model to disentangle genetic and environmental contributions to disease-related molecular changes. Herein, we investigated MZ twins who lived distinctly different lives and became discordant for AD, and analyzed which transcriptome signatures were altered in the affected twin. We further examined whether these alterations paralleled those found in sporadic AD patients compared with individuals with normal cognition (NC). Whole transcriptome sequencing was performed on mRNAs isolated from peripheral white blood cells of the discordant MZ twins, and the results were compared with transcriptome datasets from blood cells and postmortem brains of sporadic AD patients and NC subjects. In the AD twin, transcripts associated with inflammatory and immune responses were up-regulated, whereas transcripts related to signal recognition particle-mediated protein targeting pathways were down-regulated. Biological network analysis revealed dense connectivity among up-regulated genes linked to cell chemotaxis, cytokine production, and inflammatory response. Heatmap analysis demonstrated differential expression of transcripts related to histone, DNA, and RNA modifications in the AD twin. Comparative analyses with transcriptome data from postmortem brains of sporadic AD patients confirmed similarly up-regulated inflammatory responses in both groups. Taken together, these findings suggest that environmental factors can shape transcriptome signatures related to inflammation and immune pathways, and that such gene expression alterations may ultimately contribute to AD development.
(Copyright © 2025. Published by Elsevier B.V.)

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.