Systemic inflammatory markers in ageing, Alzheimer's disease and other dementias

Abstract

Systemic inflammation with alterations in inflammatory markers is involved in ageing and Alzheimer's disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during ageing and Alzheimer's disease, and specific markers contributing to Alzheimer's disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical Alzheimer's disease, 154) and a cross-sectional cohort (cohort 2: n = 351; controls, 62; Alzheimer's disease, 63; vascular dementia, 58; Parkinson's disease dementia, 56; behavioural variant frontotemporal dementia, 57; dementia with Lewy bodies, 55) were included. Plasma levels of inflammatory markers were measured every 2 years during a 10-year follow-up in the longitudinal cohort and once in the cross-sectional cohort. The study demonstrated that the inflammatory markers significantly altered during both ageing and the development of Alzheimer's disease. However, only complement C3, interleukin-1β and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their longitudinal changes were significantly associated with the development of Alzheimer's disease compared to controls over the 10-year follow-up. In the cross-sectional cohort, complement C3 demonstrated specificity to Alzheimer's disease, while interleukin-1β and interleukin-6 were also altered in other dementias. The study provides a new perspective on the involvement of inflammatory markers in the ageing process and the development of Alzheimer's disease, implying that regulating inflammation may have a pivotal role in promoting successful ageing and in the prevention and treatment of Alzheimer's disease.

Keywords: Alzheimer’s disease; ageing; complement; interleukin; longitudinal; systemic inflammation.