Quantifying natural amyloid plaque accumulation in the continuum of Alzheimer's disease using ADNI.

Brain amyloid beta neuritic plaque accumulation is associated with an increased risk of progression to Alzheimer's disease (AD) [Pfeil, J., et al. in Neurobiol Aging 106: 119-129, 2021].

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.

Strength and Deformation Behavior of Graphene Aerogel of Different Morphologies.

Graphene aerogels are of high interest nowadays since they have ultralow density, rich porosity, high deformability, and good adsorption. In the present work, three different morphologies of graphene aerogels with a honeycomb-like structure are considered. The strength and deformation behavior of these graphene honeycomb structures are studied by molecular dynamics simulation.

Prediction of Zn(V, Nb, Ta)N Monolayers for Optoelectronic Applications.

A new family of ternary nitride materials, Zn(V, Nb, Ta)N monolayers, is predicted. A fabrication mechanism of the Zn(V, Nb, Ta)N monolayers is proposed based on the chemical vapor deposition approach used for their bulk counterparts. The calculations show that these monolayers are thermodynamically and environmentally stable and that the ZnVN monolayer is the most stable and the easiest to synthesize.

ApoE4 and Connectivity-Mediated Spreading of Tau Pathology at Lower Amyloid Levels.

Importance: For the Alzheimer disease (AD) therapies to effectively attenuate clinical progression, it may be critical to intervene before the onset of amyloid-associated tau spreading, which drives neurodegeneration and cognitive decline. Time points at which amyloid-associated tau spreading accelerates may depend on individual risk factors, such as apolipoprotein E ε4 (ApoE4) carriership, which is linked to faster disease progression; however, the association of ApoE4 with amyloid-related tau spreading is unclear.

Objective: To assess if ApoE4 carriers show accelerated amyloid-related tau spreading and propose amyloid positron emission tomography (PET) thresholds at which tau spreading accelerates in ApoE4 carriers vs noncarriers.

Phylogenetic Characterization of Rabies Virus Field Isolates Collected from Animals in European Russian Regions in 2009-2022.

Rabies is a fatal disease of mammals that poses a high zoonotic risk to humans as well. The distribution of rabies is mainly driven by host animal migration and human-mediated dispersion. To contribute to the global understanding of the rabies virus (RABV) molecular epidemiology, 94 RABV field isolates collected from animals in 13 European Russian regions were phylogenetically characterized using the nearly full-size N gene nucleotide sequences.

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial.

Background: Zagotenemab (LY3303560), a monoclonal antibody, preferentially binds to extracellular, misfolded, aggregated tau that has been implicated in Alzheimer's disease (AD).

Objective: The goal of this study was to assess the safety and pharmacokinetics of multiple doses of zagotenemab in participants with AD.

Methods: This was a Phase Ib, multi-site, participant- and investigator-blind, placebo-controlled, parallel-group study in participants with mild cognitive impairment due to AD or mild to moderate AD.

Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease.

Objective: We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum.

Methods: We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, F-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas.

The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partners Scientific Board (PPSB).

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) encompasses members from industry, biotechnology, diagnostic, and non-profit organizations that have until recently been managed by the Foundation for the National Institutes of Health (FNIH) and provided financial and scientific support to ADNI programs. In this article, we review some of the major activities undertaken by the PPSB, focusing on those supporting the most recently completed National Institute on Aging grant, ADNI3, and the impact it has had on streamlining biomarker discovery and validation in Alzheimer's disease. We also provide a perspective on the gaps that may be filled with future PPSB activities as part of ADNI4 and beyond.

Tau as a diagnostic instrument in clinical trials to predict amyloid in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is characterized by the presence of both amyloid and tau pathology. In vivo diagnosis can be made with amyloid and tau positron emission tomography (PET) imaging. Emergent evidence supports that amyloid and tau accumulation are associated and that amyloid accumulation may precede that of tau.

Longitudinal head-to-head comparison of C-PiB and F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer's disease.

Purpose: Pittsburgh Compound-B (C-PiB) and F-florbetapir are amyloid-β (Aβ) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aβ monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aβ radiotracers were used. To study the consequences of using different Aβ radiotracers to measure Aβ clearance, we performed a head-to-head comparison of C-PiB and F-florbetapir in a Phase 2/3 clinical trial of anti-Aβ monoclonal antibodies.

Novel Alzheimer's disease locus identified by genome-wide association analysis of cerebral tau deposition on PET.

Determining the genetic architecture of Alzheimer's disease (AD) pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we performed a genome-wide association study of cortical tau quantified by positron emission tomography in 3,136 participants from 12 independent studies. The locus was associated with tau deposition.

Preclinical PET Imaging and Toxicity Study of a Ga-Functionalized Polymeric Cardiac Blood Pool Agent.

Cardiac blood pool imaging is currently performed almost exclusively with Tc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope Ga is used, it can be applied repeatedly on the same day-for example, for the detection of bleeding.

Prediction and Characterization of Two-Dimensional ZnVN.

A two-dimensional (2D) monolayer of a novel ternary nitride ZnVN is computationally designed, and its dynamical and thermal stability is demonstrated. A synthesis strategy is proposed based on experimental works on production of ternary nitride thin films, calculations of formation and exfoliation energies, and molecular dynamics simulations. A comprehensive characterization of 2D ZnVN, including investigation of its optoelectronic and mechanical properties, is conducted.

Metal/Graphene Composites: A Review on the Simulation of Fabrication and Study of Mechanical Properties.

Although carbon materials, particularly graphene and carbon nanotubes, are widely used to reinforce metal matrix composites, understanding the fabrication process and connection between morphology and mechanical properties is still not understood well. This review discusses the relevant literature concerning the simulation of graphene/metal composites and their mechanical properties. This review demonstrates the promising role of simulation of composite fabrication and their properties.

Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease.

Background: Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline.