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
Review
. 2025 Jun 30;16(7):782.
doi: 10.3390/genes16070782.

Intron Retention and Alzheimer's Disease (AD): A Review of Regulation Genes Implicated in AD

Ayman El-Seedy  1 , Véronique Ladevèze  2
Affiliations
Review

Intron Retention and Alzheimer's Disease (AD): A Review of Regulation Genes Implicated in AD

Ayman El-Seedy et al. Genes (Basel). .

Abstract

Determining the genetic variations of candidate genes in affected subjects will help identify early pathological biomarkers of Alzheimer's disease (AD) and develop effective treatments. It has recently been found that some genes that are linked share an increase in intron retention (IR). In this review, we discuss a few instances of mRNA-IR in various genes linked to AD, including APOE, MAPT-Tau, Psen2, Farp1, Gpx4, Clu, HDAC4, Slc16a3, and App genes. These genes are vulnerable to IR, encompassing additional crucial proteins for brain functionality, but they are frequently involved in pathways linked to the control of mRNA and protein homeostasis. Despite the advancements in human in vivo RNA therapy, as far as we know, there are no reports of data generated regarding artificial in vivo splicing in either animal models or humans. To prevent genetic variations and improve or repair errors in expression of desired genes, humans have adopted new gene editing techniques like CRISPR-Cas9 and RNAi modalities. Ultimately, IR could be utilized as a therapeutic potential biomarker for disorders related to intronic expansion.

Keywords: AD-associated genes; Alzheimer’s disease (AD); a potential diagnostic biomarker; aging; alternative splicing; intron retention.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Genes associated with increased or decreased risk for Alzheimer’s disease in human.
See this image and copyright information in PMC

References

    1. Kumar A., Sidhu J., Lui F., Tsao J.W. StatPearls [Internet] StatPearls Publishing; Treasure Island, FL, USA: 2025. Alzheimer Disease.
    1. Bekris L.M., Yu C.E., Bird T.D., Tsuang D.W. Genetics of Alzheimer disease. J. Geriatr. Psychiatry Neurol. 2010;23:213–227. doi: 10.1177/0891988710383571. - DOI - PMC - PubMed
    1. Belgrader P., Cheng J., Zhou X., Stephenson L.S., Maquat L.E. Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life. Mol. Cell. Biol. 1994;14:8219–8228. - PMC - PubMed
    1. Monteuuis G., Wong J.L., Bailey C.G., Schmitz U., Rasko J.J. The changing paradigm of intron retention: Regulation, ramifications and recipes. Nucleic Acids Res. 2019;47:11497–11513. doi: 10.1093/nar/gkz1068. - DOI - PMC - PubMed
    1. Adusumalli S., Ngian Z.K., Lin W.Q., Benoukraf T., Ong C.T. Increased intron retention is a post-transcriptional signature associated with progressive aging and Alzheimer’s disease. Aging Cell. 2019;18:e12928. doi: 10.1111/acel.12928. - DOI - PMC - PubMed