Though distinct pathological entities, corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share multiple biochemical and genetic features suggesting overlapping pathophysiology. We report the case of a patient with an 18-year clinical course consistent with behavioral variant frontotemporal dementia. The neuropathological assessment revealed unclassifiable frontotemporal lobar degeneration with tau-immunoreactive inclusions sharing features of both CBD and PSP. Whole-genome sequencing revealed a unique combination of pleiotropic genetic risk variants associated with both PSP and CBD. These findings support the observation that CBD and PSP share genetic co-expression networks that influence neurodegenerative pathogenesis common to 4R tauopathies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137543 | PMC |
| http://dx.doi.org/10.1080/13554794.2021.1879869 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.
J Neuropathol Exp Neurol
December 2024
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA).
View Article and Find Full Text PDFIron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms.
Redox Biol
December 2024
Department of Pathology and Medical Biology, University Medical Centre Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce.
View Article and Find Full Text PDFCo-pathologies modify hippocampal protein accumulation patterns in neurodegenerative diseases.
Alzheimers Dement
December 2024
Department of Laboratory Medicine and Pathobiology and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Introduction: Limited research has extensively analyzed neurodegenerative disease-related protein deposition patterns in the hippocampus.
Methods: This study examined the distribution of proteins in hippocampal subregions across major neurodegenerative diseases and explored their relation to each other. The area density of phosphorylated tau (p-tau), amyloid beta (Aβ), α-synuclein, and phosphorylated TDP-43 protein deposits together with pyramidal cell density in each hippocampal subregion, including CA1-4, prosubiculum (ProS), and subiculum was assessed in 166 cases encompassing various neurodegenerative diseases.
Two novel variants in GRN: the relevance of CNV analysis and genetic screening in FTLD patients with a negative family history.
J Neurol
December 2024
Department of Neurology and Alzheimer Centre, Erasmus MC University Medical Centre (Erasmus MC), Dr. Molenwaterplein 40, 3015 CE, Rotterdam, The Netherlands.
Background: Frontotemporal lobar degeneration (FTLD) is one of the leading causes of early onset dementia. Pathogenic variants in GRN have been reported to cause 5-25% of familial and 5% of sporadic FTLD. Here, we present two novel, likely pathogenic variants in GRN.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by the presence of extracellular amyloid plaques consisting of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (pTau) protein in the brain. Genetic and animal studies strongly indicate that Aβ, tau and neuroinflammation play important roles in the pathogenesis of AD. Several staging models showed that NFTs correlated well with the disease progression.
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!