Summary: A new study uncovers a biological mechanism that links chronic viral infection to cognitive decline and accelerated aging. Researchers found that the breakdown of anti-inflammatory sugar molecules called glycans drives persistent systemic inflammation in people living with HIV. In preclinical models, drugs that block glycan-degrading enzymes preserved these protective sugars, reduced neuroinflammation, slowed markers of biological aging, and protected memory circuits.
Using sialidase inhibitors — a class of drugs best known for treating influenza, such as oseltamivir (Tamiflu) — investigators prevented the loss of glycans in cellular and mouse models. The results suggest a promising therapeutic direction to address cognitive impairment and inflammaging associated with long-term viral infections.
Key Facts
- Persistent cognitive deficits: Roughly 25% or more of people living with HIV experience memory and cognitive impairment despite effective antiretroviral therapy.
- Glycan degradation drives inflammation: The study identifies degradation of protective glycans on blood proteins as a key pathological process that transforms regulated immune responses into chronic inflammation, accelerating biological aging.
- Human cohort evidence: Blood profiles from more than 100 HIV-positive participants in the AIDS Clinical Trials Group linked glycan loss to clinically confirmed cognitive decline.
- Drug repurposing strategy: Sialidase inhibitors, which normally block a viral enzyme, were used here to inhibit host enzymes that remove anti-inflammatory glycans, preserving their protective function.
- Preclinical efficacy: In laboratory and mouse models, sialidase inhibitors maintained glycan structures, lowered inflammatory markers, reversed features of premature aging, and preserved learning and memory.
- Sex differences and menopause: Glycan loss follows different trajectories by sex: men show a steady age-related decline, while women maintain stronger anti-inflammatory glycan profiles until a rapid shift toward pro-inflammatory states around menopause.
- Translational goals: Lead investigator Dr. Mohamed Abdel-Mohsen emphasizes the need for further preclinical optimization to determine safe and effective dosing, duration, and biomarker strategies before testing long-term neuroprotective use in humans.
Source: Northwestern University
Overview
A Northwestern University–led investigation, beginning with blood samples from people with HIV and extending into laboratory and animal studies, identifies glycan degradation as an actionable mechanism behind cognitive decline and inflammaging in chronic viral infection. The findings, published in the journal Med, point to a potential new therapeutic approach for brain and aging-related complications of chronic viral disease, with possible implications for wider neurodegenerative disorders.
The research team identified a clear association between loss of protective glycans and cognitive impairment by profiling glycan patterns on blood proteins from over 100 people with HIV, all of whom were receiving antiretroviral therapy. Subsequent experiments used immune cells derived from people with HIV and mouse models to demonstrate that glycan loss increases inflammatory signaling. Treatment with sialidase inhibitors in mice preserved the protective sugars, lowered inflammation, mitigated hallmarks of accelerated aging, and prevented memory deficits in behavioral tests.
Sialidase inhibitors such as oseltamivir are conventionally prescribed to combat influenza by blocking a viral enzyme required for viral spread. In this study, investigators repurposed that drug class to inhibit host sialidase enzymes that remove sialic-acid-containing glycans from proteins. By limiting glycan degradation, the drugs maintained an anti-inflammatory glycan shield on blood proteins and reduced downstream inflammatory processes that harm the brain.
Sex-specific findings
Sex differences emerged clearly: women in the study showed a more abrupt transition from anti-inflammatory to pro-inflammatory glycan profiles coinciding with menopause, whereas men exhibited a more gradual decline across the lifespan. This distinct trajectory suggests that women living with chronic viral infections may be particularly vulnerable to rapid inflammaging and cognitive risk during midlife hormonal transitions.
Next steps and clinical implications
The investigators are pursuing two parallel translational objectives: refining sialidase inhibitor regimens in preclinical models to establish optimal agents, doses, and treatment schedules, and developing blood-based glycan biomarkers that predict future cognitive decline. Although some sialidase inhibitors are approved for short-term influenza treatment, their safety and efficacy for chronic use to prevent neuroinflammation or cognitive decline remain untested. Careful preclinical and clinical evaluation will be necessary before any change to medical practice.
Key Questions Answered
A: By targeting a different set of enzymes in the body. Instead of blocking a viral enzyme, these drugs can inhibit human sialidase enzymes that remove protective glycans. Preserving those glycans helps keep harmful, brain-aging inflammation under control.
A: Menopause is linked to a rapid decline in anti-inflammatory glycan defenses. Before menopause, women retain stronger anti-inflammatory glycan profiles; around menopause, the protective glycan coating can degrade quickly, accelerating pro-inflammatory processes.
A: No. While the findings are promising, sialidase inhibitors have not been tested for this indication, dose, or duration in humans. The research team is conducting further preclinical work to determine safety, dosing, and predictive biomarkers before any clinical recommendations.
Editorial Notes
- This article was edited by a Neuroscience News editor.
- The underlying journal paper was reviewed in full by the editorial team.
- Additional context was provided by staff editors.
About this research
Author: Ben Schamisso
Source: Northwestern University
Contact: Ben Schamisso, Northwestern University
Image credit: Neuroscience News
Original Research: “Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment” by Leila B. Giron et al., published in Med. DOI: 10.1016/j.medj.2026.101175. The study is closed access.
Abstract (summary)
People living with HIV can develop cognitive problems even when antiretroviral therapy effectively suppresses viral replication. This study shows that individuals with cognitive impairment have greater loss of protective glycans on blood proteins, a pattern especially pronounced in women. In mouse models, blocking glycan removal reduced inflammation, slowed aging-related changes, and prevented memory decline. These results point to glycan preservation as both a potential biomarker and a therapeutic strategy to limit brain and aging-related complications of chronic viral infection.