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Article type: Research Article
Authors: Zhang, Li-Yaa | Wang, Duo-Zib | Wang, Jianc | Guo, Leib | Li, Bing-Hub; * | Wang, Jian-Hongb; *
Affiliations: [a] Department of Neurology, 363 Hospital, Chengdu, Sichuan Province, China | [b] Department of Neurology, The Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People’s Hospital, Chengdu, SichuanProvince, China | [c] Department of Neurology, Ya’an People’s Hospital, Ya’an, Sichuan Province, China
Correspondence: [*] Correspondence to: Bing-Hu Li and Jian-Hong Wang, Department of Neurology, The Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan Province, China. E-mail: libinghu1982@163.com, jhwangneurology@yeah.net.
Abstract: Background: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. Objective:This study aims to investigate the association of circulating LL-37 with longitudinal cognitive decline and neurodegeneration among older adults with memory complaints. Methods: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. Results: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. Conclusion:These findings support an association of the antimicrobial peptide LL-37 with AD from a clinical perspective.
Keywords: Alzheimer’s disease, Amyloid-β, antimicrobial peptide LL-37, cognitive decline, infection, neurodegeneration, neurofilament light, tau
DOI: 10.3233/JAD-230007
Journal: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 595-603, 2023
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