ABBA Letter Alternation: A telehealth inspired measure of executive functioning/inhibitory control.

To introduce ABBA Letter Alternation (ABBA) as a computerized measure of response inhibition/response alternation developed for telehealth following restrictions of in-person testing due to COVID-19. ABBA consists of two PowerPoint-administered trials: Letter Reading of 25 capital As or Bs individually presented, and Letter Alternation with instructions to say the opposite letter to what is presented. We obtained initial normative ABBA performance from 899 healthy research volunteers participating in the Emory Healthy Brain Study (EHBS) with Montreal Cognitive Assessment (MoCA) scores 24/30 and higher.

A single vector system for tunable and homogeneous dual gene expression in Escherichia coli.

Expression of recombinant genes can be controlled using inducible promoters. However, the most commonly used IPTG- and arabinose-inducible promoters result in an 'all-or-nothing' response, leading to fully induced and uninduced bacterial subpopulations. Here, we investigate whether appropriate modifications to these promoter systems can be combined into a single vector system, enabling homogenous expression of two genes of interest that can be precisely tuned using inducer concentration.

Technology literacy and access to digital resources for remote assessment among adults enrolled in Alzheimer's disease research.

Background: The SARS-CoV-2 pandemic accelerated development of innovative methods for conducting research remotely via digital technologies. However, few studies have examined participant technological literacy skills or access as key social determinants of brain health in aging populations at risk of Alzheimer's disease and other dementias.

Objective: To identify associations of sociodemographic and clinical characteristics, cognitive status and geolocation with digital technology access and skill within dementia research cohorts.

Receptive vocabulary is superior to education level to account for Black and White neuropsychological performance discrepancies.

Objective: To evaluate the impact of receptive vocabulary versus years of education on neuropsychological performance of Black and White older adults.

Method: A community-based prospectively enrolled cohort ( = 1,007; 130 Black, 877 White) in the Emory Healthy Brain Study were administered the NIH Toolbox Picture Vocabulary Test and neuropsychological measures. Group differences were evaluated with age, sex, and education or age, sex, and Toolbox Vocabulary scores as covariates to determine whether performance differences between Black versus White participants were attenuated or eliminated.

Simplifying Complex Figure scoring: Data from the Emory Healthy Brain Study and initial clinical validation.

Objective: To introduce the Emory 10-element Complex Figure (CF) scoring system and recognition task. We evaluated the relationship between Emory CF scoring and traditional Osterrieth CF scoring approach in cognitively healthy volunteers. Additionally, a cohort of patients undergoing deep brain stimulation (DBS) evaluation was assessed to compare the scoring methods in a clinical population.

Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups.

Methods: Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis.

Accelerated model-based T1, T2* and proton density mapping using a Bayesian approach with automatic hyperparameter estimation.

Purpose: To achieve automatic hyperparameter estimation for the model-based recovery of quantitative MR maps from undersampled data, we propose a Bayesian formulation that incorporates the signal model and sparse priors among multiple image contrasts.

Theory: We introduce a novel approximate message passing framework "AMP-PE" that enables the automatic and simultaneous recovery of hyperparameters and quantitative maps.

Methods: We employed the variable-flip-angle method to acquire multi-echo measurements using gradient echo sequence.

Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.

Introduction: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD.

Methods: To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors.

Thermodynamic Origin of the Linear Pressure Dependence of DNA Thermal Stability.

High pressure affects the structure and function of DNA and is a key parameter for studying the origin and physical limits of life. Different types of DNA structures systematically show a linear pressure dependence of thermal stability (up to ∼200 MPa), which is maintained even when the solution composition is changed. The reasons behind the linear pressure dependence are not understood.

Network proteomics of the Lewy body dementia brain reveals presynaptic signatures distinct from Alzheimer's disease.

Lewy body dementia (LBD), a class of disorders comprising Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), features substantial clinical and pathological overlap with Alzheimer's disease (AD). The identification of biomarkers unique to LBD pathophysiology could meaningfully advance its diagnosis, monitoring, and treatment. Using quantitative mass spectrometry (MS), we measured over 9,000 proteins across 138 dorsolateral prefrontal cortex (DLPFC) tissues from a University of Pennsylvania autopsy collection comprising control, Parkinson's disease (PD), PDD, and DLB diagnoses.

In vivo magnetogenetics for cell-type-specific targeting and modulation of brain circuits.

Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized.

Lower Prevalence of Asymptomatic Alzheimer's Disease Among Healthy African Americans.

Objective: Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals.

Methods: We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.

Proteomic analysis of Alzheimer's disease cerebrospinal fluid reveals alterations associated with ε4 and atomoxetine treatment.

Alzheimer's disease (AD) is currently defined by the aggregation of amyloid-β (Aβ) and tau proteins in the brain. Although biofluid biomarkers are available to measure Aβ and tau pathology, few markers are available to measure the complex pathophysiology that is associated with these two cardinal neuropathologies. Here, we characterized the proteomic landscape of cerebrospinal fluid (CSF) changes associated with Aβ and tau pathology in 300 individuals using two different proteomic technologies-tandem mass tag mass spectrometry and SomaScan.

An interim exploratory proteomics biomarker analysis of a phase 2 clinical trial to assess the impact of CT1812 in Alzheimer's disease.

CT1812 is a novel, brain penetrant small molecule modulator of the sigma-2 receptor (S2R) that is currently in clinical development for the treatment of Alzheimer's disease (AD). Preclinical and early clinical data show that, through S2R, CT1812 selectively prevents and displaces binding of amyloid beta (Aβ) oligomers from neuronal synapses and improves cognitive function in animal models of AD. SHINE is an ongoing phase 2 randomized, double-blind, placebo-controlled clinical trial (COG0201) in participants with mild to moderate AD, designed to assess the safety and efficacy of 6 months of CT1812 treatment.

Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid.

Introduction: Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types.

Methods: We conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control (N = 28), progressive supranuclear palsy (PSP) (N = 18), and AD (N = 21) cases.

Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial.

Importance: Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD).

Objective: To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment.

Design, Setting, And Participants: From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD.

Mixture of regressions with multivariate responses for discovering subtypes in Alzheimer's biomarkers with detection limits.

There is no gold standard for the diagnosis of Alzheimer's disease (AD), except from autopsies, which motivates the use of unsupervised learning. A mixture of regressions is an unsupervised method that can simultaneously identify clusters from multiple biomarkers while learning within-cluster demographic effects. Cerebrospinal fluid (CSF) biomarkers for AD have detection limits, which create additional challenges.

Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.

Introduction: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD.

Methods: To bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors.

Alzheimer's disease cerebrospinal fluid biomarkers and kidney function in normal and cognitively impaired older adults.

Introduction: Recent Alzheimer's disease (AD) clinical trials have used cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests that AD risk is related to impaired renal function. The impact of kidney function on commonly used AD biomarkers remains unknown.

Fuzzy recognition by the prokaryotic transcription factor HigA2 from Vibrio cholerae.

Disordered protein sequences can exhibit different binding modes, ranging from well-ordered folding-upon-binding to highly dynamic fuzzy binding. The primary function of the intrinsically disordered region of the antitoxin HigA2 from Vibrio cholerae is to neutralize HigB2 toxin through ultra-high-affinity folding-upon-binding interaction. Here, we show that the same intrinsically disordered region can also mediate fuzzy interactions with its operator DNA and, through interplay with the folded helix-turn-helix domain, regulates transcription from the higBA2 operon.