The role of interleukin-33 in patients with mild cognitive impairment and Alzheimer’s disease

Alzheimer’s Research & Therapy

Chia-Lin Tsai¹  Chia-Kuang Tsai¹  Guan-Yu Lin¹  Kuan-Pin Su²  Chih-Sung Liang³  Hsuan-Te Chu³  Che-Sheng Chu⁴  Ta-Chuan Yeh⁵  Yu-Kai Lin⁶  Jiunn-Tay Lee⁶  Fu-Chi Yang⁶  Ming-Wei Su⁷ 

[1] Department of Neurology, Tri-Service General Hospital, National Defense Medical Center;Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital;Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center;Department of Psychiatry, Kaohsiung Veterans General Hospital;Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center;Graduate Institute of Medical Sciences, National Defense Medical Center;Institute of Biomedical Sciences, Academia Sinica;

关键词: Cytokine;    Interleukin-33;    Alzheimer’s disease;    Mild cognitive disorder;    Cognitive decline;   

DOI  :  10.1186/s13195-020-00652-z

来源: DOAJ

【 摘 要 】

Abstract Background The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains 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) completed two Mini-Mental State Examinations (MMSEs) over a 1-year interval. In all 100 participants at the second MMSE, we 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; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. 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). 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 ApoE ε4, while higher levels of ApoE 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 (90.9% vs 53.3%, P = 0.04). Conclusions IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD.

【 授权许可】

Unknown