A study of 357 older adults with memory complaints found that people with higher blood levels of the antimicrobial peptide LL‑37 were more likely to experience faster memory loss and higher levels of brain‑damage markers over two years.

A potential role of the antimicrobial peptide LL-37, which is upregulated after infection, in the pathogenesis of Alzheimer's disease (AD) was identified. However, the clinical relevance of LL-37 in AD is not clear yet. This study aims to investigate the association of circulating LL-37 with longitudinal cognitive decline and neurodegeneration among older adults with memory complaints. This cohort study recruited 357 older adults with memory complaints. Participants were followed-up for two years and the cognitive functions were assessed using the Mini-Mental State Examination (MMSE). Serum LL-37, pTau181, and tTau levels were determined at baseline. Associations of baseline LL-37 with longitudinal cognitive decline and change of neurodegenerative biomarkers were analyzed. No difference was found in the slope of longitudinal cognitive decline during follow-up between the low and high LL-37 group, adjusting for age, sex, education, body mass index, APOE ɛ4 carrier status, comorbidities, and baseline MMSE scores (difference in slope: 0.226, 95% CI: -0.169 to 0.621). Higher LL-37 levels were associated with longitudinal cognitive decline, as indicated by a decrease of MMSE scores of 3 points or above during follow-up (OR = 2.11, 95% CI: 1.32 to 3.38). The high LL-37 group had larger slopes of the increase in neurofilament light (difference in slope: 3.759, 95% CI: 2.367 to 5.152) and pTau181 (difference in slope: 0.325, 95% CI: 0.151 to 0.499) than the low LL-37 group. These findings support an association of the antimicrobial peptide LL-37 with AD from a clinical perspective.