Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias

Abstract

ObjectivesThere is growing evidence for the role of systemic inflammation in Alzheimer’s disease (AD) and other neurodegenerative diseases; however the systemic inflammatory profile in dementia with Lewy bodies (DLB) has never before been investigated. This study aimed to characterise systemic inflammatory mediators in established DLB and AD, as well as in their prodromal, mild cognitive impairment (MCI) phases.MethodsWe obtained plasma samples from patients with DLB (n=37), AD (n=20), MCI with DLB profile (n=38), MCI with AD profile (n=20) and healthy control subjects (n=20). The following inflammatory biomarkers were measured using Roche cobas c702 and Meso Scale Discovery V-Plex Plus: high-sensitivity C-reactive protein, interferon-gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL-2, IL-4, IL-6, IL-8 and tumour necrosis factor-alpha.ResultsWe found significantly higher levels of IL-10, IL-1beta, IL-4 and IL-2 in both MCI groups (P<0.001), while there was no significant difference in inflammatory markers between dementia groups and controls. Furthermore, increased disease severity was associated with lower levels of IL-1beta, IL-2 and IL-4 (P<0.05).InterpretationWe have shown for the first time that in both DLB and AD, increased peripheral inflammation occurs early at the MCI disease stages. These data support a role for inflammation early in the disease process, and have important implications for the stage of disease where trials of anti-inflammatory medication should be focused.

Prevalence and severity of symptoms suggestive of gastroparesis in prodromal dementia with Lewy bodies

“…As described previously, 17,18,20 four symptoms, and evidence of decline which was a characteristic of AD with no evidence for another aetiology, i.e. they met the additional criterion of 'aetiology of MCI consistent with AD pathophysiologic process').…”

Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease

“…It has been shown in previous studies that inflammation occurs early in MCI-AD and MCI-DLB, and inflammation decreases as disease progresses to dementia, 16 suggesting that anti-inflammatory medications may be of use in early stages of disease in these patients. It has been shown in previous studies that inflammation occurs early in MCI-AD and MCI-DLB, and inflammation decreases as disease progresses to dementia, 16 suggesting that anti-inflammatory medications may be of use in early stages of disease in these patients.…”

“…16 In the current study, we aimed to investigate this further in patients with PD-MCI. 16 In the current study, we aimed to investigate this further in patients with PD-MCI.…”

“…Furthermore, as IL-2 is generally considered to be proinflammatory and IL-4 anti-inflammatory, there may also be a complex disruption to the balance of pro-and anti-inflammatory cytokines, particularly in the early stages of disease. 16 A longitudinal study found that increased levels of IL-6 increases the risk of PD, suggesting that inflammation occurs at the predementia stage. In AD, studies have shown that inflammation occurs at the predementia stages, 12 and the level of inflammation seems to decrease with disease progression.…”

Neuroinflammation as a potential therapeutic target in dementia with Lewy bodies

“…In their  JNNP  paper, King et al 3 present the results of a study investigating peripheral inflammation markers in plasma samples from 37 patients with DLB, 20 patients with AD dementia, 38 patients with mild cognitive impairment (MCI) and DLB profile, 20 patients with MCI and AD profile and 20 normal controls. This study indicated that increased peripheral inflammation occurs at the MCI stages and disappears with disease progression in both DLB and AD.…”