Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.

Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.

Predicting regional tau accumulation with machine learning-based tau-PET and advanced radiomics.

Introduction: Alzheimer's disease is partially characterized by the progressive accumulation of aggregated tau-containing neurofibrillary tangles. Although the association between accumulated tau, neurodegeneration, and cognitive decline is critical for disease understanding and clinical trial design, we still lack robust tools to predict individualized trajectories of tau accumulation. Our objective was to assess whether brain imaging biomarkers of flortaucipir-positron emission tomography (PET), in combination with clinical and genomic measures, could predict future pathological tau accumulation.

Tau-network mapping of domain-specific cognitive impairment in Alzheimer's disease.

Fibrillar tau gradually progresses in the brain during the course of Alzheimer's disease (AD). However, the contribution of tau accumulation in a given brain region to decline in different cognitive domains and thus phenotypic heterogeneity in AD remains unclear. Here, we leveraged the functional connectome to link the locality of tau accumulation to domain-specific cognitive impairment.

Delocalized nonlinear vibrational modes and discrete breathers in β-FPUT simple cubic lattice.

The problem of finding various discrete breathers (DBs) in the β-Fermi-Pasta-Ulam-Tsingou simple cubic lattice is addressed. DBs are obtained by imposing localizing functions on delocalized nonlinear vibrational modes (DNVMs) having frequencies above the phonon spectrum of the lattice. Among 27 DNVMs with the wave vector at the boundary of the first Brillouin zone there are three satisfying this condition.