Visual hallucinations are a core feature of dementia with Lewy bodies. Their pathophysiology is not well understood, because neither clinical nor histological data have shown their basic mechanisms. Here, we report the presence of pale inclusions in the outer plexiform layer of the retina in a patient with dementia with Lewy bodies. These inclusions are related to cytoskeletal disorganization of the cones at ultrastructural level and modifications of the immunohistochemical pattern of distribution of synucleins in the retina. These modifications may participate in the visual impairment in dementia with Lewy bodies.
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http://dx.doi.org/10.1002/ana.10730 | DOI Listing |
Brain Behav
January 2025
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Background: Neurodegenerative diseases involve progressive neuronal dysfunction and cognitive decline, posing substantial global challenges. Although the precise causes remain unclear, several studies highlight the role of protein metabolism abnormalities in disease development. This study investigates the causal links between variations in mitochondrial protein genes and neurodegenerative diseases, aiming to elucidate their potential contributions to disease progression and identify novel therapeutic strategies.
View Article and Find Full Text PDFMov Disord
January 2025
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Background: Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.
Objectives: To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.
Nat Commun
January 2025
NMR Based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.
View Article and Find Full Text PDFAlzheimers Dement (Amst)
January 2025
Biochemistry and Molecular Biology Department Neurodegenerative Pathologies LBMMS Hospices Civils de Lyon Lyon France.
Introduction: Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility in routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents to facilitate its clinical implementation.
View Article and Find Full Text PDFGeroscience
January 2025
ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France.
The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort.
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