Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With AD, PSP, and CBS

This parallel-design, double-blind randomized clinical trial assesses the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 in patients with Alzheimer disease or the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome.
Source: JAMA Neurology - Category: Neurology Source Type: research

Related Links:

AbstractThe diagnostic workflow of patients with cognitive decline needs an extensive clinical evaluation. The use of FDG-PET can be helpful because the finding of a rather specific pattern of hypometabolism could point to specific neurodegenerative disorders. In patients with memory impairment and visuo-spatial deficits, FDG-PET may reveal a pattern of temporo-parietal hypometabolism that is associated with Alzheimer ’s disease or a more extended area of hypometabolism that spreads to the occipital cortex, as in posterior cortical atrophy indicating signs of neurodegeneration in the associative visual cortex. In the...
Source: Clinical and Translational Imaging - Category: Radiology Source Type: research
ConclusionsSimilar to AD, the interpretation of [18F]THK5351 uptake in PSP is likely confounded by off-target binding to MAO-B binding sites. [18F]THK5351 is not sufficient in quantifying tau aggregates in PSP using the proposed rasagiline dosing regimen.
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
AbstractThe term “propagon” is used to define proteins that may transmit misfolding in vitro, in tissues or in organisms. Among propagons, misfolded tau is thought to be involved in the pathogenic mechanisms of various “tauopathies” that include Alzheimer's disease, progressive supranuclear palsy, and argyro philic grain disease. Here, we review the available data in the literature and point out how the prion-like tau propagation has been extended from Alzheimer's disease to tauopathies. First, in Alzheimer’s disease, the progression of tau aggregation follows stereotypical anatomical stages w...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
In Alzheimer's disease (AD) and tauopathies, tau aggregation accompanies progressive neurodegeneration. Aggregated tau appears to spread between adjacent neurons and adjacent brain regions by prion-like seeding. Hence, inhibitors of this seeding offer a possible route to managing tauopathies. Here, we report the 1.0 Å resolution micro-electron diffraction structure of an aggregation-prone segment of tau with the sequence SVQIVY, present in the cores of patient-derived fibrils from AD and tauopathies. This structure illuminates how distinct interfaces of the parent segment, containing the sequence VQIVYK, foster the f...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Protein Structure and Folding Source Type: research
This article reviews advances in the diagnosis, epidemiology, pathology, hypothesized etiopathogenesis, and biomarkers and disease-modifying therapeutic approaches of PSP that is leading it to become a frontrunner in translation.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
AbstractTo address the need for more meaningful biomarkers of tauopathies, we have developed an ultrasensitive tau seed amplification assay (4R RT-QuIC) for the 4-repeat (4R) tau aggregates of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and other diseases with 4R tauopathy. The assay detected seeds in 106–109-fold dilutions of 4R tauopathy brain tissue but was orders of magnitude less responsive to brain with other types of tauopathy, such as from Alzheimer ’s disease cases. The analytical sensitivity for synthetic 4R tau fibrils was ~ 50 fM or 2 fg/sample. A n...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer ’s disease, progressive supranuclear palsy, and chronic traumatic encephalopathy. 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 com position, and affected cell types seen across these disorders. In this review, we describe and discuss recent evidence from human postmortem and clinical biomarker studies addressing the differential...
Source: Biological Psychiatry - Category: Psychiatry Authors: Tags: Review Source Type: research
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.
Source: Biological Psychiatry - Category: Psychiatry Authors: Tags: Review Source Type: research
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.
Source: Alzheimer Disease and Associated Disorders - Category: Geriatrics Tags: Original Articles Source Type: research
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]
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
More News: Alzheimer's | Brain | Clinical Trials | Neurology | Progressive Supranuclear Palsy