Hee-Ju Kang1, Jae-Min Kim1, Sung-Wan Kim1, Il-Seon Shin1, Sung-Woo Park2, Young-Hoon Kim2, Jin-Sang Yoon1. 1. Department of Psychiatry, Depression Clinical Research Centre, Chonnam National University Medical School, Gwangju, Korea. 2. Department of Neuropsychiatry, School of Medicine, Haeundae Paik Hospital, Paik Institute for Clinical Research & FIRST research group, Inje University, Busan, Korea.
Abstract
BACKGROUND: Inflammatory processes regulated by cytokines are important in the aetiology of Alzheimer's disease (AD) and depression. Differences in transcriptional activities associated with several genetic polymorphisms affect cytokine production. We investigated the involvement of alleles associated with higher production of proinflammatory and lower production of anti-inflammatory cytokines in AD and depression in a community-dwelling sample of elderly individuals. METHOD: A total of 732 community-dwelling elders were clinically evaluated for AD applying the NINCDS-ADRDA criteria and for depression applying the Geriatric Mental State Schedule. Genotyping was performed for six proinflammatory (interleukin (IL)-1β -511C/T and +3953C/T, IL-6 -174G/C, IL-8 -251T/A, tumour necrosis factor (TNF)-α -850C/T) and two anti-inflammatory (IL-4 +33T/C, IL-10 -1082G/A) cytokines. The sums of risk alleles of proinflammatory and anti-inflammatory cytokine genes were estimated. Age, gender, education and apolipoprotein E genotype were considered covariates. RESULTS: TNF-α -308G/A and IL-8 -251T/A were significantly associated with AD and IL-1β +3953C/T with late-life depression, while the significance of these associations was lost after Bonferroni correction. A greater number of risk alleles producing proinflammatory cytokines was significantly associated with AD, but not with depression, after adjustment for the covariates. No association was found between an increased number of risk alleles for anti-inflammatory cytokine production and either AD or depression. CONCLUSIONS: The present findings support the inflammatory hypothesis in the aetiology of AD as measured by several cytokine genes associated with increased proinflammatory cytokine production. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND: Inflammatory processes regulated by cytokines are important in the aetiology of Alzheimer's disease (AD) and depression. Differences in transcriptional activities associated with several genetic polymorphisms affect cytokine production. We investigated the involvement of alleles associated with higher production of proinflammatory and lower production of anti-inflammatory cytokines in AD and depression in a community-dwelling sample of elderly individuals. METHOD: A total of 732 community-dwelling elders were clinically evaluated for AD applying the NINCDS-ADRDA criteria and for depression applying the Geriatric Mental State Schedule. Genotyping was performed for six proinflammatory (interleukin (IL)-1β -511C/T and +3953C/T, IL-6-174G/C, IL-8-251T/A, tumour necrosis factor (TNF)-α -850C/T) and two anti-inflammatory (IL-4+33T/C, IL-10-1082G/A) cytokines. The sums of risk alleles of proinflammatory and anti-inflammatory cytokine genes were estimated. Age, gender, education and apolipoprotein E genotype were considered covariates. RESULTS: TNF-α -308G/A and IL-8-251T/A were significantly associated with AD and IL-1β +3953C/T with late-life depression, while the significance of these associations was lost after Bonferroni correction. A greater number of risk alleles producing proinflammatory cytokines was significantly associated with AD, but not with depression, after adjustment for the covariates. No association was found between an increased number of risk alleles for anti-inflammatory cytokine production and either AD or depression. CONCLUSIONS: The present findings support the inflammatory hypothesis in the aetiology of AD as measured by several cytokine genes associated with increased proinflammatory cytokine production. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: D C Steffens; M E Garrett; K L Soldano; D R McQuoid; A E Ashley-Koch; G G Potter Journal: Int Psychogeriatr Date: 2020-07-09 Impact factor: 3.878