Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review

Abstract

Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.

Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer’s disease: a cross-sectional metabolomic analysis

“…The list of changes included putrescine synthesis, triglyceride homeostasis [TG (16:0_40:8), TG(18:1_38:7), TG(18:3_38:6)], and for sphingomyelin hydroxylation [SM-OH/SM-Non OH 24:1 and SM-OHs/SM-Non OHs]. Interestingly, these significantly correlated with GFAP, which is proposed to reflect neuroinflammation in the early stages of neurodegenerative disease ( Surendranathan et al, 2018 ; Hansson, 2021 ; Loveland et al, 2023 ).…”

The role of immune inflammatory response and inflammatory infiltrates in major depression disorder and atopic dermatitis: new insights from machine learning

“…Previous studies elucidated a complex interplay between the immune and nervous systems, commonly referred to as immune-neural regulation (Maximova et al, 2021). During this regulation, astrocytes and microglia can generate and release inflammation-related cytokines, potentially affecting neuronal activity and function (Loveland, Yu, Churilov, Yassi, & Watson, 2023). This immune-neural regulation may exhibit abnormalities in individuals with AD and MDD, impairing the nervous system function(X.…”

Evidence for prodromal changes in neuronal excitability and neuroinflammation in the hippocampus in young alpha-synuclein (A30P) transgenic mice

“…Activated microglia also release reactive oxygen/nitrogen species such as nitric oxide (NO) produced via inducible nitric oxide synthase (iNOS). Elevated iNOS in both neurons and microglia has been seen in post-mortem LBD patient's brains and mouse models of PD (Stykel and Ryan, 2022 ; Loveland et al, 2023 ). In DLB microglia activation has been proposed to occur early in the prodromal phase of the disease progression.…”