Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau
Abstract Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer’s disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7–18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243–406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau.
The International Parkinson Disease and Movement Disorder Society PSP study group (IPMDS-PSP) recently published new clinical diagnostic criteria for progressive supranuclear palsy (PSP). Currently, there is no data regarding the accuracy of these sets of criteria for differentiating various PSP phenotypes. We discuss the accuracy of the IPMDS-PSP criteria for differentiation of patients with the PSP- Richardson phenotype (PSP-RS) from those with the PSP-Parkinsonism (PSP-P) using data from a sample of 274 clinically diagnosed PSP patients participating in the Environmental Genetic PSP (ENGENE-PSP) case control study.
CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients. PMID: 31591837 [PubMed]
Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer ’s disease (AD), progressive supranuclear palsy (PSP), and chronic traumatic encephalopathy (CTE). A growing body of literature suggests that conformational characteristics of tau filaments, along with regional vulnerability to tau pathology, account for the distinct histopathological morphologies , biochemical composition and affected cell types seen across these disorders.
Substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is frequent in Parkinson's disease (PD), while lenticular nucleus hyperechogenicity (LN+) and 3rd ventricle enlargement (3V+) are typical of Atypical Parkinsonisms (AP). However, there are no studies assessing the diagnostic yield of all TCS biomarkers in the three AP (progressive supranuclear palsy, PSP, multiple system atrophy, MSA, corticobasal degeneration, CBD). Previous references lack homogeneous criteria and data are incomprehensive.
Authors: Sorbera C, Portaro S, Cimino V, Leo A, Accorinti M, Silvestri G, Bramanti P, Naro A, Calabrò RS Abstract Progressive supranuclear palsy (PSP) is a neurodegenerative disease of the central nervous system, presenting with different clinical phenotypes, all involving the extrapyramidal system. Orthostatic hypotension (OH) is a common symptom of cardiovascular autonomic dysfunction. OH is defined as a fall in systolic blood pressure of at least 20 mmHg and/or a fall in diastolic blood pressure of at least 10 mmHg on standing or head-up tilt. In this pilot study, we tested the feasibility and efficacy of...
Abstract Objective: Progressive supranuclear palsy (PSP) is associated with a variety of cognitive deficits, but few studies have reported on its cognitive trajectory across time, especially on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Methods: Two hundred twenty participants diagnosed with Richardson's syndrome of PSP (PSP-RS) were evaluated with the RBANS at baseline, six months, and one year with alternate forms. Results: When using dependent t-tests, significant declines were observed on all Indexes of the RBANS from baseline to six months (ps
Condition: Progressive Supranuclear Palsy Interventions: Other: gait recordings; Other: brain magnetic resonance imaging; Other: oculomotor movement recordings Sponsors: Centre Hospitalier Universitaire de Pointe-a-Pitre; University Hospital Center of Martinique; Groupe Hospitalier Pitie-Salpetriere Completed
The microtubule-associated protein tau undergoes aberrant modification resulting in insoluble brain deposits in various neurodegenerative diseases, including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal degeneration. Tau aggregates can form in different cell types of the central nervous system (CNS) but are most prevalent in neurons. We have previously recapitulated aspects of human FTD in mouse models by overexpressing mutant human tau in CNS neurons, including a P301S tau variant in TAU58/2 mice, characterized by early-onset and progressive behavioral deficits and FTD-like neuropatholog...
CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases. PMID: 31513029 [PubMed - as supplied by publisher]
ConclusionQSM could be used for iron quantification of nigral and extranigral structures in all degenerative parkinsonisms and should be tested longitudinally in order to identify early microscopical changes.