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Background: Inflammation plays a key role in the aetiology and progression of Alzheimer's disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly. We hypothesised that, using blood biomarkers, DLB would show an increased proinflammatory profile compared with controls, and that there would be a distinct profile compared with AD.
Methods: 93 participants (31 with DLB, 31 with AD and 31 healthy older controls) completed a single study visit for neuropsychiatric testing and phlebotomy. Peripheral blood mononuclear cells were quantified for T and B cell subsets using flow cytometry, and serum cytokine concentrations were measured using multiplex immunoassay.
Results: We detected reduced relative numbers of helper T cells and reduced activation of B cells in DLB compared with AD. Additionally, interleukin (IL)-1β was detected more frequently in DLB and the serum concentration of IL-6 was increased compared with controls.
Conclusions: Peripheral inflammation is altered in DLB compared with AD, with T cell subset analysis supporting a possible shift towards senescence of the adaptive immune system in DLB. Furthermore, there is a proinflammatory signature of serum cytokines in DLB. Identification of this unique peripheral immunophenotype in DLB could guide development of an immune-based biomarker and direct future work exploring potential immune modulation as a novel treatment.
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http://dx.doi.org/10.1136/jnnp-2020-323603 | DOI Listing |
Parkinsonism Relat Disord
September 2025
Translational and Clinical Research Institute, Newcastle University, UK.
Introduction: Dysfunction of the glymphatic system is thought to lead to build up of toxic proteins including β-amyloid and α-synuclein, and thus may be involved in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) index has been proposed as a marker of glymphatic function.
Aims: To investigate DTI-ALPS in mild cognitive impairment (MCI) and dementia, and determine its relationship with cognitive decline, and biomarkers of neurodegeneration.
Neurology
October 2025
Montreal Neurological Institute-Hospital, McGill University, Montreal, Canada.
Background And Objectives: Years before diagnosis of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA), mild prodromal manifestations can be detected. Longitudinal follow-up of people with prodromal synucleinopathy, particularly idiopathic/isolated REM sleep behavior disorder (iRBD), enables in-depth clinical phenotyping of early disease, which could facilitate stratification for clinical trials, provide the definition of appropriate end points, or predict phenoconversion more precisely. The aim of this study was to update and expand on previous studies assessing clinical evolution from iRBD to clinically diagnosed disease, up to 14 years before diagnosis.
View Article and Find Full Text PDFNeurology
October 2025
Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Fundació Recerca Clínic Barcelona-IDIBAPS, Spain.
Background And Objectives: α-Synuclein seed amplification assays (αSAAs) can improve the diagnosis of synucleinopathies and detect α-synuclein (αSyn) copathology in vivo in clinical practice. We aimed to evaluate the diagnostic performance of αSAA for detecting αSyn in CSF for diagnosing dementia with Lewy bodies (DLB) in a clinical cohort of cognitively impaired individuals. We explored how the coexistence of Alzheimer disease (AD) and αSyn pathology influences biomarker levels and clinical profiles.
View Article and Find Full Text PDFLancet
August 2025
Department of Anesthesia, St Michael's Hospital-Unity Health Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, Univ
Background: Saphenous vein graft (SVG) failure remains a substantial challenge after coronary artery bypass graft (CABG). LDL cholesterol (LDL-C) is a causal risk factor for atherosclerosis, but its role in SVG failure is not well established. We evaluated whether early initiation of intensive LDL-C lowering with evolocumab could reduce SVG failure.
View Article and Find Full Text PDFBrain
September 2025
Dementia Research Centre, University College London, London, WC1N 3AR, UK.
Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are subtypes of Lewy body dementia, and are considered two ends of a disease spectrum. However, conventional MRI neuroimaging, mainly focussed on grey matter volume and thickness, has failed to establish whether underlying processes differ between them. Understanding these differences could enable targeted and subtype-specific treatments to be developed.
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