Browsing by Subject "Lewy body disease"

Now showing 1 - 3 of 3
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    Complete Evaluation of Dementia: PET and MRI Correlation and Diagnosis for the Neuroradiologist
    (American Society of Neuroradiology, 2021) Oldan, J. D.; Jewells, V. L.; Pieper, B.; Wong, T. Z.; Radiology and Imaging Sciences, School of Medicine
    This article will familiarize neuroradiologists with the pathophysiology, clinical findings, and standard MR imaging and PET imaging features of multiple forms of dementia as well as new emerging techniques. Cases were compiled from multiple institutions with the goal of improved diagnostic accuracy and improved patient care as well as information about biomarkers on the horizon. Dementia topics addressed include the following: Alzheimer disease, frontotemporal dementia, cerebral amyloid angiopathy, Lewy body dementia, Parkinson disease and Parkinson disease variants, amyotrophic lateral sclerosis, multisystem atrophy, Huntington disease vascular dementia, and Creutzfeldt-Jakob disease.
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    Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies
    (Springer Nature, 2024-01-05) Reho, Paolo; Saez-Atienzar, Sara; Ruffo, Paola; Solaiman, Sultana; Shah, Zalak; Chia, Ruth; Kaivola, Karri; Traynor, Bryan J.; Tilley, Bension S.; Gentleman, Steve M.; Hodges, Angela K.; Aarsland, Dag; Monuki, Edwin S.; Newell, Kathy L.; Woltjer, Randy; Albert, Marilyn S.; Dawson, Ted M.; Rosenthal, Liana S.; Troncoso, Juan C.; Pletnikova, Olga; Serrano, Geidy E.; Beach, Thomas G.; Easwaran, Hariharan P.; Scholz, Sonja W.; Pathology and Laboratory Medicine, School of Medicine
    Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.
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    Lewy Body Disease is a Contributor to Logopenic Progressive Aphasia Phenotype
    (Wiley, 2021) Buciuc, Marina; Whitwell, Jennifer L.; Kasanuki, Koji; Graff-Radford, Jonathan; Machulda, Mary M.; Duffy, Joseph R.; Strand, Edythe A.; Lowe, Val J.; Graff-Radford, Neill R.; Rush, Beth K.; Franczak, Malgorzata B.; Flanagan, Margaret E.; Baker, Matthew C.; Rademakers, Rosa; Ross, Owen A.; Ghetti, Bernardino F.; Parisi, Joseph E.; Raghunathan, Aditya; Reichard, R. Ross; Bigio, Eileen H.; Dickson, Dennis W.; Josephs, Keith A.; Pathology and Laboratory Medicine, School of Medicine
    Objective: The objective of this study was to describe clinical features, [18 F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) metabolism and digital pathology in patients with logopenic progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB). Methods: This is a clinicopathologic case-control study of 45 patients, including 20 prospectively recruited patients with LPA among whom 6 were diagnosed with LPA-DLBD. We analyzed clinical features and compared FDG-PET metabolism in LPA-DLBD to an independent group of patients with clinical pDLB and regional α-synuclein burden on digital pathology to a second independent group of autopsied patients with DLBD pathology and antemortem pDLB (DLB-DLBD). Results: All patients with LPA-DLBD were men. Neurological, speech, and neuropsychological characteristics were similar across LPA-DLBD, LPA-Alzheimer's disease (LPA-AD), and LPA-frontotemporal lobar degeneration (LPA-FTLD). Genetic screening of AD, DLBD, and FTLD linked genes were negative with the exception of APOE ε4 allele present in 83% of LPA-DLBD patients. Seventy-five percent of the patients with LPA-DLBD showed a parietal-dominant pattern of hy pometabolism; LPA-FTLD - temporal-dominant pattern, whereas LPA-AD showed heterogeneous patterns of hypometabolism. LPA-DLBD had more asymmetrical hypometabolism affecting frontal lobes, with relatively spared occipital lobe in the nondominantly affected hemisphere, compared to pDLB. LPA-DLBD had minimal atrophy on gross brain examination, higher cortical Lewy body counts, and higher α-synuclein burden in the middle frontal and inferior parietal cortices compared to DLB-DLBD. Interpretation: Whereas AD is the most frequent underlying pathology of LPA, DLBD can also be present and may contribute to the LPA phenotype possibly due to α-synuclein-associated functional impairment of the dominant parietal lobe.