ALZHEIMER’S disease (AD), a neurodegenerative condition marked by cognitive decline and progressive memory loss, has long been associated with chronic inflammation and immune dysregulation. Regulatory T cells (Tregs), key modulators of immune tolerance, are known to be impaired in individuals with AD. A recent study explored whether low-dose Interleukin-2 (IL-2), a cytokine known to expand Treg populations, could safely and effectively modulate immune response and disease progression in patients with AD. Notably, the treatment was found to stabilise cerebrospinal fluid (CSF) levels of Aβ42, a biomarker closely linked to Alzheimer’s pathology.
In a phase 2a, randomised, double-blind, placebo-controlled trial, 38 participants with AD received subcutaneous IL-2 at a dose of 10⁶ IU/day for five consecutive days. They were allocated to two dosing regimens: every four weeks (IL-2 q4wks, n=9) or every two weeks (IL-2 q2wks, n=10), while 19 received placebo. The treatment period lasted 21 weeks, followed by a nine-week observation phase. Primary outcomes focused on safety and adverse events, while secondary and exploratory endpoints assessed immunological, biochemical, and clinical responses.
All participants completed the trial without serious adverse events or deaths, supporting IL-2’s safety profile. Both IL-2 regimens increased Treg counts and their suppressive function, with the q4wks group showing a stronger effect, including increased Foxp3 expression. IL-2 q4wks also significantly reduced pro-inflammatory mediators CCL2, CCL11, and IL-15, while increasing anti-inflammatory markers such as IL-4. Crucially, this group showed a statistically significant rise in CSF Aβ42 levels (p=0.045 vs. placebo), a favourable sign of disease modification. Additionally, neurofilament light (NfL), a marker of neurodegeneration, remained stable in the IL-2 q4wks group but increased in the placebo arm. The adjusted mean change in ADAS-cog scores suggested slower cognitive decline with IL-2 q4wks, though this did not reach statistical significance (p=0.061).
These findings highlight low-dose IL-2, particularly with four-weekly administration, as a promising and safe immunotherapy for AD, capable of shifting immune balance and altering disease biomarkers. However, the small sample size and short duration limit the generalisability of these results. Larger, longer-term trials are needed to confirm clinical benefits, but these data offer a potential new direction for immune-based interventions in Alzheimer’s care.
Reference
Faridar A et al. Low-dose interleukin-2 in patients with mild to moderate Alzheimer’s disease: a randomized clinical trial. Alzheimers Res Ther. 2025;17(1):146
