Background: The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).
Objective: To investigate the association between CNVs and structural forms on 17q.
Introduction: Early-onset Parkinson's Disease (EOPD) is a neurodegenerative disease with the clinical manifestation of movement symptoms before the age of 50. Patients with EOPD frequently have a positive family history of disease, with bi-allelic loss of function mutations in PRKN and PINK1 as the most common genetic cause. To date, the majority of genetic studies have been conducted on patients with European ancestry, limiting the understanding of the genetic heterogeneity of EOPD across populations.
View Article and Find Full Text PDFIntroduction: Clinicopathological correlations differ by sex in Lewy body dementia (LBD). However, previous studies have focused on pathological staging systems that place less emphasis on regional pathologies.
Methods: We included 357 people (131 female, 226 male) with a high likelihood of LBD based on pathology from the Brain Bank for Neurodegenerative (Jacksonville, FL).
Purpose: This study examined occupational histories in multiple system atrophy to identify environmental associations of potential relevance to disease causation.
Methods: A total of 270 neuropathologically confirmed cases of multiple system atrophy obtained from the Mayo Clinic Brain Bank for neurodegenerative disorders in Jacksonville, Florida, were included in this case-control study. Demographic and disease information was collected from medical records.
Mutations in leucine-rich repeat kinase 2 () are the most common cause of familial and sporadic Parkinson's disease (PD). While the clinical features of -PD patients resemble those of typical PD, there are significant differences in the pathological findings. The pathological hallmark of definite PD is the presence of α-synuclein (αSYN)-positive Lewy-related pathology; however, approximately half of -PD cases do not have Lewy-related pathology.
View Article and Find Full Text PDFBackground: Microbial dysbiosis has been reported to contribute to development of neurodegenerative diseases, however, there is a need to identify causative/prognostic indicators.
Objectives: To comparatively analyze gut microbiome composition in symptomatic LBD (dementia/mild cognitive impairment), iRBD, and cohabiting controls without LBD or iRBD.
Methods: 16S rRNA amplicon sequencing was performed in 38 cases (27 LBD, 11 iRBD) and 39 cohabitant controls.
Neurol Neuroimmunol Neuroinflamm
November 2024
Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.
View Article and Find Full Text PDFAggregated α-synuclein (α-SYN) proteins, encoded by the gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we recapitulated α-SYN pathologies in human induced pluripotent stem cells (iPSCs)-derived cortical organoids generated from patients with LBD with gene triplication.
View Article and Find Full Text PDFProgressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored.
View Article and Find Full Text PDFMitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial genome (mtDNA) has been shown to acquire potentially damaging somatic variation as part of the aging process, while mtDNA single nucleotide polymorphism (SNPs) have been shown to be both protective and detrimental for various neurodegenerative diseases. Yet, little is known about the involvement of mtDNA variation in longevity and successful neurological aging.
View Article and Find Full Text PDFBackground: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2.
Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID.
Pregnancy in women with early-onset Parkinson's disease (PD) is likely to have a higher frequency given the trend toward increasing maternal age, thus resulting in a greater overlap time between childbearing age and PD risk. Deep brain stimulation (DBS) therapy is nowadays offered to PD patients at earlier stage of the disease, when women can still be pre-menopausal. However, few data are available about DBS safety during pregnancy.
View Article and Find Full Text PDFFrontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.
View Article and Find Full Text PDFLewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by α-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, AD is characterized by amyloid plaques and neurofibrillary tangles.
View Article and Find Full Text PDFDespite substantial progress, causal variants are identified only for a minority of familial Parkinson's disease (PD) cases, leaving high-risk pathogenic variants unidentified. To identify such variants, we uniformly processed exome sequencing data of 2,184 index familial PD cases and 69,775 controls. Exome-wide analyses converged on RAB32 as a novel PD gene identifying c.
View Article and Find Full Text PDFBackground: Obstructive sleep apnea (OSA) is increasingly recognized as a common condition in the general population and causes significant OSA-associated morbidities including cardiovascular and cerebrovascular events such as cerebral small vessel disease (CSVD) and stroke.
Methods: In this study, using sensitive ELISA immunoassays, we measured subset of endothelial/vascular and inflammatory biomarkers as well as neurofilament light chain (NfL), a sensitive marker for neuroaxonal injury, using plasma from OSA patients post-stroke (Acute Cerebral Infarction (ACI), N = 26) to determine their usefulness as potential prognostic markers in disease progression.
Results: Our results showed significantly increased plasma TNFα and NfL concentrations and decreased concentrations of platelet derived growth factor (PDGF-AA) in post-stroke OSA patients with more severe white matter hyperintensities (WMHs).
Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement.
Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy.
Design, Setting, And Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020.