Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis.
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http://dx.doi.org/10.1111/j.1742-4658.2008.06709.x | DOI Listing |
Lancet Neurol
February 2025
Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada; Department of Cognitive Neurology, St Joseph's Health Care London, London, ON, Canada. Electronic address:
Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.
View Article and Find Full Text PDFParkinsonism Relat Disord
January 2025
Department of Nuclear Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:
Introduction: In isolated REM sleep behavior disorder (iRBD), the evidence of cognitive impairment and co-existing amyloid pathology suggests that mild behavioral impairment (MBI) may be associated with disease progression. In this study, we investigated MBI and its association with cognitive function, brain amyloid load and glucose metabolism in iRBD patients to evaluate the utility of MBI as a predictive marker of disease progression.
Methods: Patients with iRBD underwent a neuropsychological evaluation, F-florbetaben (FBB) PET, and F-fluorodeoxyglucose (FDG) PET.
Neurobiol Dis
January 2025
Department of Physiology and Pharmacology "Vittorio Erspamer", The Sapienza University of Rome, Rome, Italy; Hospital San Raffaele Cassino, Cassino, FR, Italy.
Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) and low alpha (8-10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.
Introduction: Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification.
Methods: We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRS ), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls.
Metab Brain Dis
January 2025
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Hale Building for Transformative Medicine, Room 10006, 60 Fenwood Road, Boston, MA, 02115, USA.
α-Synuclein (αS) is a 140 amino-acid neuronal protein highly enriched in presynaptic nerve terminals. Its progressive accumulation in Lewy bodies and neurites is the hallmark of Parkinson's disease (PD). A growing number of studies highlights a critical interplay between lipid metabolism and αS biology.
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