Flu drugs point to a new path against memory loss

Clinical takeaway: Glycan degradation may help explain why cognitive problems persist in well-treated HIV and could eventually serve to identify at-risk patients. Repurposing flu antivirals to preserve these sugars is a preclinical proof of concept, not yet a treatment.

Cognitive impairment remains common in people with HIV even when antiretroviral therapy fully suppresses the virus, affecting at least a quarter of patients, and the reasons have stayed murky. This study points to a culprit that sits upstream of the usual inflammatory suspects: the breakdown of protective sugar chains, or glycans, on circulating proteins. Sialic acid and galactose, two glycans with anti-inflammatory roles, normally keep immune signaling in check; their loss is a known hallmark of biological aging.

Those patients with cognitive impairment showed more glycan degradation, and the degree of loss tracked with worse cognitive scores across two cohorts. Eleven conventional inflammatory markers, including IL-6 and TNF-α, did not separate impaired from unimpaired patients, while the glycan changes did, suggesting glycomic state is a more sensitive readout of cognitive status than the cytokines clinicians usually examine. The association was strongest in women, an asymmetry the authors tie to estrogen's known effects on glycosylation and the acceleration of glycan loss around menopause.

The human data are associational, so the team turned to mice to test causality. In a humanized model of HIV and a second model built to allow cognitive testing, a combination of the flu antiviral oseltamivir and an experimental sialidase inhibitor preserved sialylation, blunted inflammation, and slowed markers of epigenetic aging.

In the cognitive model, treated animals were protected from the learning and memory deficits that infection otherwise produced. The drugs worked not by blocking the virus, but by stopping sialidases, the host enzymes that strip sialic acid off glycans, a previously unrecognized anti-inflammatory action for a familiar drug class.

Because glycan loss is a shared feature of aging across cardiovascular disease, cancer, and neurodegeneration, the authors suggest preserving sialylation could matter beyond HIV, in other chronic inflammatory and age-related conditions.

The team is now working on two fronts: refining the drug approach and testing whether glycan signatures can predict who will decline, rather than just marking who already has. Because the existing antivirals inhibit human sialidases only weakly, next-generation compounds built for that target may matter more than the flu drugs themselves.

"We are not saying yet that people should take flu drugs to prevent cognitive decline," said lead author Mohamed Abdel-Mohsen, PhD, of Northwestern University Feinberg School of Medicine. "We are saying that our findings open the door to testing whether this drug class, or better next-generation versions, could be repurposed for brain and aging-related complications."

Source: Giron LB, et al. Med. 2026 Jun 5. Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment