Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Oct 21;14(1):24717.
doi: 10.1038/s41598-024-75431-z.

A meta-analysis of bulk RNA-seq datasets identifies potential biomarkers and repurposable therapeutics against Alzheimer's disease

Anika Bushra Lamisa #  1   2 , Ishtiaque Ahammad #  2 , Arittra Bhattacharjee #  2 , Mohammad Uzzal Hossain  2 , Ahmed Ishtiaque  1 , Zeshan Mahmud Chowdhury  2 , Keshob Chandra Das  3 , Md Salimullah  3 , Chaman Ara Keya  4
Affiliations
Meta-Analysis

A meta-analysis of bulk RNA-seq datasets identifies potential biomarkers and repurposable therapeutics against Alzheimer's disease

Anika Bushra Lamisa et al. Sci Rep. .

Erratum in

Abstract

Alzheimer's disease (AD) poses a major challenge due to its impact on the elderly population and the lack of effective early diagnosis and treatment options. In an effort to address this issue, a study focused on identifying potential biomarkers and therapeutic agents for AD was carried out. Using RNA-Seq data from AD patients and healthy individuals, 12 differentially expressed genes (DEGs) were identified, with 9 expressing upregulation (ISG15, HRNR, MTATP8P1, MTCO3P12, DTHD1, DCX, ST8SIA2, NNAT, and PCDH11Y) and 3 expressing downregulation (LTF, XIST, and TTR). Among them, TTR exhibited the lowest gene expression profile. Interestingly, functional analysis tied TTR to amyloid fiber formation and neutrophil degranulation through enrichment analysis. These findings suggested the potential of TTR as a diagnostic biomarker for AD. Additionally, druggability analysis revealed that the FDA-approved drug Levothyroxine might be effective against the Transthyretin protein encoded by the TTR gene. Molecular docking and dynamics simulation studies of Levothyroxine and Transthyretin suggested that this drug could be repurposed to treat AD. However, additional studies using in vitro and in vivo models are necessary before these findings can be applied in clinical applications.

Keywords: Alzheimer’s disease; Biomarker; Drug discovery; RNA-Seq.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The criteria used for the selection of datasets.
Fig. 2
Fig. 2
Overall workflow of the study.
Fig. 3
Fig. 3
Volcano plot of differentially expressed genes. The upregulated and downregulated genes were depicted on the right and left respectively. The genes were indicated using yellow dots.
Fig. 4
Fig. 4
a Significantly enriched pathway of the downregulated genes by using KEGG and Reactome database; b Significantly enriched pathway of the upregulated genes by using KEGG database.
Fig. 5
Fig. 5
Protein-protein interactions network for the (a) upregulated and (b) downregulated genes in Alzheimer’s disease.
Fig. 6
Fig. 6
MicroRNA interacting genes within the network of (a) upregulated and (b) downregulated genes in Alzheimer’s disease.
Fig. 7
Fig. 7
Transcription factors and their target genes within the network of (a) upregulated and (b) downregulated genes in Alzheimer’s disease.
Fig. 8
Fig. 8
Hub genes within the network of (a) upregulated and (b) downregulated genes in Alzheimer’s disease.
Fig. 9
Fig. 9
Drug-gene interactions with the hub proteins in the network of (a) upregulated and (b) downregulated genes in Alzheimer’s disease.
Fig. 10
Fig. 10
Molecular Docking between the TTR and Levothyroxine. TTR gene interacts with Levothyroxine through Arg103A, Asp99A, Thr119A, Ala120A, Ser100A.
Fig. 11
Fig. 11
RMSD profile of apo receptor (Purple) and Levothyroxine-receptor complex (Green).
Fig. 12
Fig. 12
RMSF profile of apo receptor (Purple) and Levothyroxine-receptor complex (Green).
Fig. 13
Fig. 13
Rg profile of apo receptor (Purple) and Levothyroxine-receptor complex (Green).
Fig. 14
Fig. 14
SASA profile of apo receptor (Purple) and Levothyroxine-receptor complex (Green).
See this image and copyright information in PMC

References

    1. Bagyinszky, E., Giau, V. V. & An, S. A. Transcriptomics in Alzheimer’s Disease: aspects and challenges. Int. J. Mol. Sci. 21(10), 3517. 10.3390/ijms21103517 (2020). - PMC - PubMed
    1. Busche, M. A. & Hyman, B. T. Synergy between amyloid-β and tau in Alzheimer’s disease, Nat. Neurosci. 23(10), 1183–1193 10.1038/s41593-020-0687-6 (2020). - PMC - PubMed
    1. Alzheimer’s Association Calcium Hypothesis Workgroup and & Khachaturian, Z. S. Calcium hypothesis of Alzheimer’s disease and brain aging: a framework for integrating new evidence into a comprehensive theory of pathogenesis. Alzheimers Dement. 13(2), 178. 10.1016/j.jalz.2016.12.006 (2017). - PubMed
    1. Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P. & Kivipelto, M. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol. 9(7), 702–716. 10.1016/S1474-4422(10)70119-8 (2010). - PubMed
    1. Breijyeh, Z. & Karaman, R. Comprehensive Review on Alzheimer’s Disease: causes and treatment. Molecules. 25(24), 5789. 10.3390/molecules25245789 (2020). - PMC - PubMed

Publication types