Corticobasal syndrome and dementia with Lewy bodies are clinical presentations with unique and overlapping features but distinct pathological substrates. We report the case of an 80 year-old man who presented with apraxia, rigidity, slowness, right arm myoclonus, a 10-year history of probable REM-sleep behavior disorder, and later developed visual hallucinations. At autopsy, he had pathological features of corticobasal degeneration, and Lewy body disease confined to the brainstem. This report highlights the importance of considering co-existing pathologies when a clinical presentation defies categorization, and demonstrates that salient features of dementia with Lewy bodies may result from pathology limited to the brainstem.
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http://dx.doi.org/10.1080/13554794.2019.1604973 | DOI Listing |
Sci Rep
January 2025
Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden.
Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Colorado State University, Fort Collins, CO, USA.
Background: In tauopathies, the protein tau misfolds into a b-sheet conformation that self-templates and spreads throughout the brain causing progressive degeneration. Biological and structural data have shown that the shape, or strain, that tau adopts when it misfolds determines which disease a patient will develop. We previously used HEK293T cells expressing TauRD-YFP to show that tau strain formation is isoform-specific.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
TauC3 Biologics Limited, London, United Kingdom.
Background: Tau abnormalities are a central feature of Alzheimer's disease (AD) and the defining feature of non-AD tauopathies, which include frontotemporal lobar degeneration (FTLD) due to Pick's disease (PiD) or Mapt mutations (FTLD-tau), as well as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and others. Mapt transcripts undergo alternative splicing to produce 6 distinct isoforms. Exon 2 splicing produces 0, 1 or 2 inserts; exclusion or inclusion of exon 10 results in 3-repeat (3R) or 4-repeat (4R) forms, respectively.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan, Ann Arbor, MI, USA.
Background: Globose neurofibrillary tangles (NFTs) are found in subcortical areas of post-mortem brain from individuals with the second most common primary tauopathy, progressive supranuclear palsy (PSP). The degree of cognitive impairment in secondary tauopathies such as Alzheimer's disease (AD) correlates with the presence of NFTs, which originally appear in the entorhinal cortex before spreading throughout the hippocampus. In contrast, the degree of hippocampal tau pathology in PSP is thought to be limited, consistent with the view that cognitive impairment in PSP is predominantly subcortical.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater, FL, USA.
Background: Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) are characterized by abnormal aggregation and deposition of tau proteins in neurons and supporting brain cells. The underlying pathophysiology of these 4R-tauopathy disorders remains unclear. In Alzheimer's disease (AD), a related tauopathy, vesicle trafficking deficits, and impaired protein clearance are observed early in disease progression.
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