Interferon-induced protein IFIT3 as a molecular nexus of neuroinflammation in Alzheimer’s disease and HIV-associated neurocognitive disorders

Authors

• Ranjit Kumar Das, The University of Texas Rio Grande ValleyFollow
• Nirakar Sahoo, The University of Texas Rio Grande ValleyFollow
• Deepa Roy, The University of Texas Rio Grande ValleyFollow
• Lauren Nguyen
• Hansapani Rodrigo, The University of Texas Rio Grande ValleyFollow
• Asim K. Duttaroy
• Jerel Adam Fields
• Upal Roy, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

4-7-2026

Abstract

Alzheimer’s disease (AD) and HIV-associated neurocognitive disorder (HAND) are significant global health concerns characterized by cognitive impairment and shared pathological features, including chronic neuroinflammation, amyloid deposition, and immune dysregulation. However, the precise molecular connections between these disorders remain unclear. Here, we identify IFIT3 as a critical shared mediator of neuroinflammatory responses in both AD and HAND. Using complementary approaches, including neuronal and microglial cell cultures, the APP/PS1 mouse model, and human postmortem brain tissues, we demonstrate consistent IFIT3 upregulation in response to amyloid-beta (Aβ) and HIV-1 exposure, with notably enhanced expression under combined conditions. Treatment with combination antiretroviral therapy (cART) partially mitigated IFIT3 induction. Additionally, siRNA-mediated silencing of IFIT3 significantly reduced key inflammatory mediators, including mitochondrial antiviral signaling protein (MAVS), nuclear factor-κB, and proinflammatory cytokines. Clinically, elevated IFIT3 expression was associated with early HAND and progressively increased across advancing AD Braak stages. Together, these findings identify IFIT3 as a potential molecular bridge between HAND and AD, highlighting its promise as both a biomarker and a therapeutic target for inflammation-driven neurodegeneration.

Comments

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

Recommended Citation

Das, Ranjit Kumar, Nirakar Sahoo, Deepa Roy, et al. 2026. “Interferon-Induced Protein IFIT3 as a Molecular Nexus of Neuroinflammation in Alzheimer’s Disease and HIV-Associated Neurocognitive Disorders.” Journal of Neuroinflammation 23 (1): 112. https://doi.org/10.1186/s12974-026-03713-6

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Journal of Neuroinflammation

DOI

10.1186/s12974-026-03713-6