Pro-inflammatory cytokine genetic variants show variable susceptibility to mild cognitive impairment, alzheimer's disease and frontotemporal dementia in South India

Abstract

Dementia is a general term for loss of memory, ling and other thinking abilities that are severe enough to interfere with daily life. It is very crucial to distinguish the different forms of dementia such as Alzheimer's disease (AD), frontotemporal dementia (FTD) and amnestic mild cognitive impairment (MCI) at phenotypic and genetic level. In India, the estimated prevalence of dementia for adults more than 60 years old is reported to be 7.4%. It is known that immune response gets compromised with age and this brings the immune hypothesis into the core of neurodegeneration, that need critical investigation. To address this concern a battery of pro and anti-inflammatory cytokine gene variants was screened in patients diagnosed with AD (n = 150), FTD (n = 65) and MCI (n = 70) and compared with age-matched cognitively normal controls (n = 250) from a clinical cohort of South India (Kerala). The genotyping results show that rs1800796 GG and GC genotypes in IL-6 may confer a genetic susceptibility for AD group, whereas IL-1β, rs1143634, IL-6 promoter variants, rs1800795 (G allele) and rs1800796 (GC genotype) and three TNF variants, rs361525 (AA genotype), rs1800629 (GG genotype) and rs1799964 (CC genotype and C allele) could play an important role in the susceptibility to MCI group. In FTD, TNF promoter variant rs1800629 AA genotype showed a significant association compared to controls. These findings suggest that proinflammatory cytokine gene variations may confer variable risk for AD, MCI and FTD in the analyzed population, highlighting the need for further research to elucidate the underlying mechanisms. The environmental and inflammatory threshold are defined by genetic risk variants of inflammation. Identifying genetic risk factors for inflammation might help in defining how age and chronicity of inflammation can define and distinguish dementia and its subtypes.

Keywords: Alzheimer’s disease; Cytokines; Dementia; Frontotemporal dementia; Mild cognitive impairment; Neuroinflammation.