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 |
Sci Rep
January 2025
Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
Cognition plays a central role in the diagnosis and characterization of dementia with Lewy bodies (DLB). However, the complex associations among cognitive deficits in different domains in DLB are largely unknown. To characterize these associations, we investigated and compared the cognitive connectome of DLB patients, healthy controls (HC), and Alzheimer's disease patients (AD).
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January 2025
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, QC H3A 2B4, Canada.
Blood-based biomarkers for Alzheimer's disease (AD) pathology have been intensively investigated as markers for AD-related neurodegeneration. Comorbid AD pathology is common in dementia with Lewy bodies (DLB). Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behavior disorder (iRBD), an incipient synucleinopathy.
View Article and Find Full Text PDFMov Disord
January 2025
Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway.
CNS Neurosci Ther
January 2025
Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Objective: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD.
View Article and Find Full Text PDFFront Neurol
December 2024
Center of Autonomic and Peripheral Nerve Disorders, Beth Israel Deaconess Medical Center, Boston, MA, United States.
Introduction: The diagnosis of diseases known as synucleinopathies, Parkinson's disease (PD), multiple system atrophy (MSA) and Lewy body dementia (DLB), is predominantly based on clinical criteria. However, diagnostic uncertainty may persist until late in the disease process leading to delays in diagnosis and medical mismanagement. Skin biopsy detection of phosphorylated alpha-synuclein (P-SYN) is a sensitive and specific technique that increases diagnostic sensitivity of synucleinopathies, although the clinical utility of this test has not been fully explored.
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