Inflammation in dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). The profile of inflammation in AD has been extensively researched in recent years, with evidence that chronic peripheral inflammation in midlife increases the risk of late-onset AD, and data supporting inflammation being associated with disease progression. In contrast, our understanding of the role of inflammation in DLB is less developed. Most research to date has examined inflammation in related disorders, such as Parkinson's disease, but there is now a growing range of literature examining inflammation in DLB itself. We present a review of the literature in this field, exploring a range of research methodologies including those quantifying markers of inflammation in cerebrospinal fluid, peripheral blood, post-mortem brain tissue, and using neuroimaging and preclinical data. Our review reveals evidence from PET imaging and peripheral blood analysis to support an increase in cerebral and peripheral inflammation in mild or prodromal DLB, that dissipates with disease progression. We present evidence from post-mortem brain tissue and pre-clinical studies that indicate α-synuclein directly promotes inflammation, but that also support the presence of AD co-pathology as an important factor in the profile of neuroinflammation in DLB. We propose that specific markers of inflammation may play a sentinel role in the mild stage of the disease, particularly when combined with AD pathology. We advocate further examination of the profile of inflammation in DLB through robust longitudinal studies, to enhance our understanding of the pathogenesis of the disease. The goal should be to utilise future results to develop a composite biomarker to aid diagnosis of DLB, and to potentially identify novel therapeutic targets.

Keywords: Cytokines; Dementia with Lewy bodies; Inflammation; Microglia; Synuclein.