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The Role of Interleukin-33 in Patients with Mild Cognitive Impairment and Alzheimer's Disease
23 Pages Posted: 27 Jul 2020
More...Abstract
Objective: The neuroprotective role of Interleukin (IL)-33 is supported in numerous pre-clinical studies but remains mostly uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD.
Methods: A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) were completed twice Mini Mental State Examination (MMSE) over a 1-year interval. At the second MMSE, the 100 participants examined the plasma levels of IL-33, IL-β, IL-1 receptor agonist (IL-1RA), beta amyloid (Aβ), and tau and apolipoprotein E (ApoE) genotyping, and Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating were performed as well.
Results: IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P < 0.001). The patients expressing IL-33 preserved their cognitive function compared with IL-33 non-expressing patients (1-year ΔMMSE: 0.16 ± 1.6 vs -1.5 ± 2.6; P = 0.006). The cognitive preservation was not associated with the lower levels of Aβ, tau, and AopE ε4, while higher levels of AopE ε4 and phosphorylated tau were indeed associated with cognitive decline. The aMCI patients with AD conversion during study period had higher proportion of IL-33(-) than non-AD converters (0.9% vs 53.3%, P = 0.04).
Conclusions: IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD.
Funding Statement: Supported by grants from the Ministry of Science and Technology of Taiwan (MOST 106-2314-B-016-007-MY2, MOST 108-2314-B-016-023-), Tri-Service General Hospital (TSGH-C106-068, TSGH-C108-100, TSGH-C108-216), and Beitou Branch, Tri-Service General Hospital (TSGH-BT-108-01).
Declaration of Interests: All authors declare that there is no conflict of interest regarding the publication of this article.
Ethics Approval Statement: The protocol was approved by the Institutional Review Board for the Protection of Human Subjects at the Tri-Service General Hospital (TSGHIRB 1-107-05-111). Informed consent was obtained from all participants.
Keywords: interleukin-33; Alzheimer's disease; mild cognitive impairment; cognitive function; cytokine
Suggested Citation: Suggested Citation