Background: Alpha-synuclein is a major component of Lewy bodies (LBs) in Parkinson disease and dementia with LBs and of glial cytoplasmic inclusions in multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this are poorly understood but may reflect fundamental differences in disease mechanisms.
Objective: To investigate the alpha-synuclein epitope mapping properties of LBs in familial Alzheimer disease.
Design And Setting: We compared LBs in familial Alzheimer disease with those in synucleinopathies by probing 6 brains of persons with familial Alzheimer disease using a panel of antibodies to epitopes spanning the alpha-synuclein protein. Results were compared with data from brains of persons with Parkinson disease, dementia with LBs, and multiple system atrophy.
Results: The brains of persons with familial Alzheimer disease showed consistent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occurred in multiple system atrophy.
Conclusions: These data suggest that the epitope profiles of alpha-synuclein in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same within cell types but distinctive between cell types.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1001/archneur.58.11.1817 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exome sequencing reveals a rare damaging variant in GRIN2C in familial late-onset Alzheimer's disease.
Alzheimers Res Ther
January 2025
Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, Turin, 10126, Italy.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with both genetic and environmental factors contributing to its pathogenesis. While early-onset AD has well-established genetic determinants, the genetic basis for late-onset AD remains less clear. This study investigates a large Italian family with late-onset autosomal dominant AD, identifying a novel rare missense variant in GRIN2C gene associated with the disease, and evaluates the functional impact of this variant.
View Article and Find Full Text PDFVirtual primary care for people living with dementia in Canada: cross-sectional surveys of patients, care partners, and family physicians.
BMC Prim Care
January 2025
Department of Family Medicine, Faculty of Medicine, McGill University, 5858 Ch. de la Côte des Neiges, Montreal, QC, H3S 1Z1, Canada.
Background: Virtual care (VC) for dementia in primary care settings is an important aspect of healthcare delivery in Canada. However, the evidence informing optimal and sustainable provision of VC for persons living with dementia (PLWD) and their care partners is scarce. The objectives of this study were to (1) describe the frequency of VC use, (2) identify characteristics of PLWD, care partners, and family physicians (FPs) that are associated with the use of VC, and (3) explore FPs' perceptions of barriers and facilitators to provide VC for PLWD and their care partners.
View Article and Find Full Text PDFTargeting mitophagy in neurodegenerative diseases.
Nat Rev Drug Discov
January 2025
Mission Therapeutics Ltd, Babraham Research Campus, Cambridge, UK.
Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need.
View Article and Find Full Text PDFMulti-domain Online Therapeutic Investigation of Neurocognition (MOTION) - A randomized comparative-effectiveness study of two remotely delivered mind-body interventions for older adults with cognitive decline.
Contemp Clin Trials
January 2025
Department of Neurology, University of California, Los Angeles, United States of America.
Background: Research suggest that mind-body movement programs have beneficial effects on cognitive outcomes for older adults with cognitive decline. However, few studies have directly compared specific approaches to mind-body movement or studied the impact of remote program delivery.
Methods: In a 3-arm randomized controlled trial (RCT) for older adults with cognitive impairment, we are comparing a multidomain mind-body program that emphasizes movement, body awareness, personal meaningfulness, and social connection, and a traditional Chinese mind-body exercise (Tai Chi) to a health and wellness education control condition.
Upregulation of p52-ZER6 (ZNF398) increases reactive oxygen species by suppressing metallothionein-3 in neuronal cells.
Biochem Biophys Res Commun
January 2025
Department of Pharmacology, Republic of Korea; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 440-746, Republic of Korea; Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea. Electronic address:
ZNF398/ZER6 belongs to the Krüppel-associated box (KRAB) domain-containing zinc finger proteins (K-ZNFs), the largest family of transcriptional repressors in higher organisms. ZER6 exists in two isoforms, p52 and p71, generated through alternative splicing. Our investigation revealed that p71-ZER6 is abundantly expressed in the stomach, kidney, liver, heart, and brown adipose tissue, while p52-ZER6 is predominantly found in the stomach and brain.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!