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.

Mechanistic Insights of Gamma Sensory Stimulation: CSF Proteomic Analyses Reveal Changes in Myelin and Synaptic Proteins.

Background: Preclinical investigations in Alzheimer’s disease (AD) have highlighted the efficacy of gamma sensory stimulation in mitigating AD‐related pathologies. Cognito Therapeutics, Inc. (Cambridge, MA) has designed the Sensory Stimulation System for safe at‐home usage, to induce EEG‐confirmed gamma oscillations as a potential treatment for AD.

Proteomic Analysis Resolves Distinct Molecular Signatures in Alzheimer’s Disease Brain Across Diverse Racial Groups.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non‐Hispanic White (NHW) population. To address this, Accelerating Medicines Partnership in AD (AMP‐AD) aimed to promote inclusivity in multi‐omics AD research, to unravel unique molecular signatures and pathways. The study aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial groups.

Longitudinal Association of Perceived Stress with Cerebrospinal Fluid Alzheimer's Disease Biomarkers in a Biracial Cohort.

Background: African American (AA) persons have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White persons. Our previous cross‐sectional study (JAD, 2020, 77:843‐853) demonstrated an association between self‐reported stress levels and cerebrospinal fluid (CSF) AD biomarkers. Using a biracial cohort, the current study investigates the association between stress and longitudinal CSF AD biomarkers over time.

Association between Medical Comorbidities and White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study.

Background: Older African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease and related dementias (ADRD) compared to non‐Hispanic white (NHW) adults. AA and HA persons may also develop disease at younger ages with more rapid progression. Vascular disease, including cerebral small vessels, manifest by white matter hyperintensity (WMH) lesions, is more prevalent in AA and HA.

Alzheimer's Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults.

Background: Recent Alzheimer’s disease (AD) clinical trials have used CSF biomarker levels for screening and enrollment. Preliminary evidence suggests Alzheimer’s Disease (AD) risk may be related to impaired renal function but the association of variation in levels of biomarkers commonly used AD biomarkers with kidney function is unknown.

Method: We conducted an analysis using data from participants enrolled in two research protocols at the Goizueta Alzheimer’s Disease Research Center that had simultaneous measurements of serum creatinine at the time of their Cerebrospinal fluid (CSF) collection (N=970).

Association of Plasma Alzheimer’s Disease Biomarkers with White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study.

Background: Older African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease (AD) than older non‐Hispanic white (NHW) adults. Cerebrovascular disease reflected by white matter hyperintensity (WMH) lesions on magnetic resonance imaging (MRI) may influence ADRD risk in these groups. Amyloid and tau PET data from studies of mostly NHW participants show a relationship between AD pathology and WMH lesions.

Association between Stress and White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study.

Background: Older African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease and related dementias (ADRD) than older non‐Hispanic white (NHW) adults. Adverse experiences like stress and discrimination may contribute to the higher vascular disease burden observed in AA and HA persons. Cerebrovascular disease reflected by white matter hyperintensity (WMH) lesions on magnetic resonance imaging (MRI) may affect ADRD risk in older AA and HA adults.

Relationships Between Retinal Amyloid Imaging and Amyloid PET in the A4 Trial.

Background: Alterations to the retina manifest in patients diagnosed with neurodegenerative diseases such as Alzheimer’s disease (AD). Retinal imaging techniques open the possibility for non‐invasive evaluation of AD pathology. Clinically AD diagnosed patients exhibit retinal amyloid deposits.

Plasma pTau217 Predicts AD and Disease Progression in a Diverse Cohort.

Background: Plasma pTau217 detects AD pathology and show longitudinal changes dependent on baseline pathology. However, previous studies have been restricted to cohorts with limited diversity. We evaluated performance of plasma pTau217 in detecting AD and predicting disease progression in a diverse cohort from the Emory Goizueta ADRC.

The Association Between Pulse Wave Velocity and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease.

Background: Prior studies have demonstrated a negative correlation between arterial stiffness and cognitive function, suggesting that pulse wave velocity (PWV) could be a promising noninvasive vascular biomarker for detecting cognitive decline. However, the link between PWV and specific Alzheimer’s Disease (AD) cerebrospinal fluid (CSF) biomarkers has not been examined. This cross‐sectional study examines the association between PWV and AD CSF tau/Aβ ratios.

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.

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.

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.

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.