Presentation Details
| Upregulation of Alzheimer’s Disease-Related Genes in the Olfactory System Following Influenza Virus Infection Elias Mimouni1, 2, Akihito Kuboki1, Shaina Maitra1, 3, Cailu Lin1, Danielle R.Reed1, Peihua Jiang1, Johannes Reisert1, Haiqing Zhao4, Hong Wang1. 1Monell Chemical Senses Center, Philadelphia, PA, USA.2University of Pennsylvania, Philadelphia, PA, USA.3Haverford College, Haverford, PA, USA.4Johns Hopkins University, Baltimore, MD, USA |
Abstract
Loss of smell is one of the earliest symptoms observed in Alzheimer’s disease (AD), often preceding cognitive decline by several years, suggesting that the olfactory system may play a role in early disease pathogenesis. Viral infections, including influenza, have emerged as potential risk factors for AD and may modulate neurodegenerative pathways. However, the mechanisms linking peripheral viral infection to AD remain poorly understood. We previously demonstrated that influenza viruses can directly infect olfactory sensory neurons and induce smell loss in a mouse model. In the present study, we examine whether influenza virus infection alters the expression of AD-related genes in the olfactory epithelium (OE) and olfactory bulb (OB). RNA was isolated from the OE and OB of uninfected control mice and mice at 7, 14, and 30 days post-inoculation (dpi). RNA sequencing and quantitative RT-PCR were performed to assess gene expression changes. We observed upregulation of multiple inflammatory pathways in both the OE and OB, notably the upregulation of complement components involved in synaptic pruning. Influenza virus infection also increased the expression of Mapt and App, which encode Tau and amyloid precursor protein, respectively, two proteins whose dysregulation contributes to AD pathogenesis. Furthermore, several genes encoding kinases that phosphorylate Tau, including Mark1, Ttbk1, and Ttbk2, were significantly upregulated in olfactory tissues. Tau hyperphosphorylation is a critical step leading to Tau misfolding and the formation of insoluble filaments within neurons, a key pathological hallmark of AD. Together, these findings indicate that influenza virus infection induces AD-related pathways, particularly those associated with Tau phosphorylation, in the peripheral olfactory system.
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