Publications by authors named "Allan I Levey"
Background: Recent research has postulated that the activation of cGAS-STING-interferon signalling pathways could be implicated in the pathogenesis of Alzheimer's disease (AD). However, the precise types of interferons and related cytokines, both from the brain and periphery, responsible for cognitive impairment in patients with AD remain unclear.
Methods: A total of 131 participants (78 [59.
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.
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.
The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples.
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- - The TREAT-AD program aims to create reliable tools for testing hypotheses related to Alzheimer's disease, emphasizing the need for validated research antibodies used in experiments involving drug targets.
- - Researchers assessed several commercial antibodies targeting specific proteins (Moesin, CD44, Midkine, and sFRP-1) using Western blot analysis on brain tissues from a mouse model with Alzheimer's pathology.
- - The study found significant increases in the expression of these target proteins in the Alzheimer's model compared to control mice, confirming the antibodies' effectiveness for future research on Alzheimer's therapeutics.
Article Synopsis
- * The study successfully enriched HBPs from plasma samples of AD patients and controls, identifying 2865 proteins and observing correlations between specific plasma proteins and AD brain biomarkers, revealing complex relationships between blood and brain changes.
- * Key plasma proteins that showed elevated levels in AD, including SMOC1 and APOE4, could effectively distinguish AD from controls, with a 0.85 accuracy, and when combined with plasma pTau181, enhanced diagnostic capability.
In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups.
View Article and Find Full Text PDFIntroduction: 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.
Article Synopsis
- The study analyzed serum proteins in 5,127 older Icelandic adults to gain insights into the molecular processes of late-onset Alzheimer's disease (LOAD) over nearly 13 years.
- Researchers identified 303 proteins linked to incident LOAD, with over 40% showing independent associations from the APOE-ε4 gene variant, indicating involvement in neuronal functions.
- Four proteins were found to be downregulated by APOE-ε4 but upregulated in LOAD, suggesting they may reflect a biological response to the onset of the disease, highlighting dysregulated processes early in LOAD development.
Introduction: CT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials.
Methods: Unbiased analysis of tandem-mass tag mass spectrometry (TMT-MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC cohort (NCT03493282).
The spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) interaction has a major role in the normal innate and adaptive immune responses, but dysregulation of this interaction is implicated in several human diseases, including autoimmune disorders, hematological malignancies, and Alzheimer's Disease. Development of small molecule chemical probes could aid in studying this pathway both in normal and aberrant contexts. Herein, we describe the miniaturization of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to measure the interaction between SYK and FCER1G in a 1536-well ultrahigh throughput screening (uHTS) format.
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- Antibodies are important in scientific research, but many of them haven't been properly tested, making some research results questionable.
- There have been efforts to fix this problem, especially for antibodies that work with human proteins.
- The article suggests ways that different people and organizations, like researchers and universities, can help make sure future studies with antibodies are more reliable.
Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid β (Aβ)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aβ amyloid responsome.
View Article and Find Full Text PDFLewy 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.
View Article and Find Full Text PDFObjective: 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.
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.
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- The SYK and FCER1G proteins work together in the immune system, but problems with their interaction can lead to diseases like autoimmune issues and Alzheimer's.
- Scientists developed a special test to measure how these proteins interact, making it easier to test lots of different compounds at once.
- They found that a compound called hematoxylin can stop the interaction between SYK and FCER1G, which is exciting because it could help in finding new treatments.
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.
Article Synopsis
- Alzheimer's disease (AD) primarily affects diverse populations, but most research has focused on the non-Hispanic White demographic, necessitating a broader understanding across different racial and ethnic groups.
- This study involved analyzing brain tissues from donors of various racial backgrounds, utilizing mass spectrometry to examine protein levels in key brain regions related to AD, resulting in a large dataset of proteins associated with the disease.
- The findings highlighted significant protein elevations linked to AD across all groups, emphasizing the importance of ethnoracial-specific differences in protein expression for future research and potential treatments.
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.
Article Synopsis
- The study examines the links between air pollution, specifically fine particulate matter, and Alzheimer's disease risk indicators in cognitively healthy adults aged 45-75.
- Researchers analyzed CSF biomarkers related to Alzheimer’s using data from 1,113 participants, alongside estimated exposure to ambient and traffic-related air pollution over 1, 3, and 5 years.
- Results indicate that increased exposure to ambient air pollution correlates with lower CSF biomarker levels that may predict Alzheimer’s risk, while traffic-related pollution showed similar patterns but lacked statistical significance.
Introduction: Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to β-amyloid (Aβ) and tau pathology in Alzheimer's disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches.
Methods: We employed heparin affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to capture and enrich HBPs in plasma obtained from AD (n=62) and control (n=47) samples.
Indoor Group Identification and Localization Using Privacy-Preserving Edge Computing Distributed Camera Network.
IEEE J Indoor Seamless Position Navig
January 2024
Article Synopsis
- Social interaction behaviors can be influenced by physical and mental health issues, making it crucial to monitor group activities in clinical settings to support patient mental health.
- This study introduces a system utilizing a camera network to detect and track group formations in a therapeutic environment, providing effective localization even with imperfect data from multiple cameras.
- The method achieved high accuracy (F1 score of 90% and a mean error of 1.25 m) in identifying groups during various interactions, and is designed to be low-cost and easily integrated into existing buildings for smarter clinical monitoring.