Publications by authors named "Suzanne E. Schindler"

Amyloid-β (Aβ) positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarkers are now established tools in the diagnostic workup of patients with Alzheimer's disease (AD), and their use is anticipated to increase with the introduction of new disease-modifying therapies. Although these biomarkers are comparable alternatives in research settings to determine Aβ status, biomarker testing in clinical practice requires careful consideration of the strengths and limitations of each modality, as well as the specific clinical context, to identify which test is best suited for each patient. This article provides a comprehensive review of the pathologic processes reflected by Aβ-PET and CSF biomarkers, their performance, and their current and future applications and contexts of use.

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Unlabelled: Years of experience watching our patients progressively decline and die from complications of Alzheimer's disease (AD) has strongly motivated us to provide newly approved anti-amyloid treatments to appropriate patients. Following detailed and personalized discussions of the potential risks and benefits of these treatments with patients and their families, almost 300 patients at our clinic have chosen to receive lecanemab infusions. We have found the frequency and severity of complications, including amyloid-related imaging abnormalities (ARIA), to be manageable and as expected based on clinical trials.

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Objective: Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls.

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Introduction: For many patients and caregivers, a major goal of disease-modifying treatments (DMTs) for Alzheimer's disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.

Methods: Participants at the Knight Alzheimer Disease Research Center (Knight ADRC) who met eligibility criteria for recent DMT trials were studied: age ≥60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating [CDR] score 0.

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With the advent of treatments that specifically target Alzheimer's disease brain pathology, biomarker tests will become an increasingly important part of the routine clinical evaluation of cognitive impairment and guide clinical decision making. Clinicians must ensure they are using accurate and well-validated biomarker tests and select the most appropriate testing modality for each patient based on individual and practical considerations. The interpretation of test results may be complex and depends on the pre-test probability and test-specific factors.

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Background: We describe the Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core major activities from October 2004 to March 2024, including biobanking ADNI cerebrospinal fluid (CSF), plasma, and serum biofluid samples, biofluid analyses for Alzheimer's disease (AD) biomarkers in the Biomarker Core and various non-ADNI laboratories, and continuous assessments of pre-analytics.

Results: Validated immunoassay and mass spectrometry-based assays were performed in CSF with a shift to plasma, a more accessible biofluid, as qualified assays became available. Performance comparisons across different CSF and plasma AD biomarker measurement platforms have enriched substantially the ADNI participant database enabling method performance determinations for AD pathology detection and longitudinal assessments of disease progression.

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Introduction: In the research setting, obtaining accurate established biomarker measurements and maximizing use of the precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all the established and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA) is a technology that requires 15 µL of sample to measure more than 100 analytes.

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Plasma biomarkers for Alzheimer's disease (AD) are increasingly being used to assist in making an etiological diagnosis for cognitively impaired (CI) individuals or to identify cognitively unimpaired (CU) individuals with AD pathology who may be eligible for prevention trials. However, a better understanding of the timing of plasma biomarker changes is needed to optimize their use in clinical and research settings. The aim of this study was to evaluate the timing of change of key AD plasma biomarkers (Aβ42/Aβ40, p-tau217, p-tau181, GFAP and NfL) from six different companies, along with established AD biomarkers, using AD progression timelines based on amyloid and tau PET.

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Dementia is characterized by a decline in memory and thinking that is significant enough to impair function in activities of daily living. Patients seen in dementia specialty clinics are highly heterogenous with a variety of different symptoms that progress at different rates. Recent research has focused on finding data-driven subtypes for revealing new insights into dementia's underlying heterogeneity, rather than assuming that the cohort is homogenous.

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Background And Objectives: CSF biomarkers of Aβ42 and phosphorylated tau (p-tau181) are used clinically for the detection of Alzheimer disease (AD) pathology during life. CSF biomarker validation studies have largely used clinical diagnoses and/or amyloid PET imaging as the reference standard. The few existing CSF-to-autopsy studies have been restricted to late-stage AD.

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Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests.

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Introduction: Blood tests have the potential to improve the accuracy of Alzheimer's disease (AD) clinical diagnosis, which will enable greater access to AD-specific treatments. This study compared leading commercial blood tests for amyloid pathology and other AD-related outcomes.

Methods: Plasma samples from the Alzheimer's Disease Neuroimaging Initiative were assayed with AD blood tests from C2N Diagnostics, Fujirebio Diagnostics, ALZPath, Janssen, Roche Diagnostics, and Quanterix.

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Article Synopsis
  • Diagnosing Alzheimer's disease is tough for doctors, which can lead to delays in getting the right care for patients.
  • Blood tests that check for signs of Alzheimer's could help doctors find the disease earlier and treat it better, but there are still some big challenges to overcome.
  • A special group of leaders in Alzheimer's research is working on solutions, like creating better guidelines, training healthcare workers, and making sure patients understand their test results.
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  • Blood-based biomarkers (BBMs) are new tests that help doctors check for Alzheimer's disease in a simpler and cheaper way than older methods like brain scans or spinal fluid tests.! -
  • A special group called the Global CEO Initiative on Alzheimer's Disease is suggesting two ways to use these BBMs: one for initial testing and another to confirm more serious cases.! -
  • Using BBMs can make it easier for doctors to diagnose Alzheimer's, which means that patients can start getting needed treatments faster.!
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  • The study aimed to assess how disease-modifying treatments (DMT) for Alzheimer’s disease (AD) affect the duration of independence in daily living activities among individuals with very mild to mild AD dementia.
  • It followed 282 participants over about 2.9 years, finding that loss of independence in instrumental activities (IADLs) typically occurred when CDR-SB scores reached above 4.5, and for basic activities (BADLs) above 11.5.
  • Notably, treatments like lecanemab and donanemab were associated with extended periods of independence in IADLs, with lecanemab offering an average of 10 months and donanemab providing an average of 13
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Introduction: Biomarkers have been essential to understanding Alzheimer's disease (AD) pathogenesis, pathophysiology, progression, and treatment effects. However, each biomarker measure is a representation of the biological target, the assay used to measure it, and the variance of the assay. Thus, biomarker measures are difficult to compare without standardization, and the units and magnitude of effect relative to the disease are difficult to appreciate, even for experts.

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Introduction: Plasma has been proposed as an alternative to cerebrospinal fluid (CSF) for measuring Alzheimer's disease (AD) biomarkers, but no studies have analyzed in detail which biofluid is more informative for genetics studies of AD.

Method: Eleven proteins associated with AD (α-synuclein, apolipoprotein E [apoE], CLU, GFAP, GRN, NfL, NRGN, SNAP-25, TREM2, VILIP-1, YKL-40) were assessed in plasma (n = 2317) and CSF (n = 3107). Both plasma and CSF genome-wide association study (GWAS) analyses were performed for each protein, followed by functional annotation.

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Article Synopsis
  • Phase 3 trials have shown that antiamyloid therapies are more effective in patients with milder Alzheimer disease, highlighting the need for plasma biomarkers in screening cognitively unimpaired individuals at risk of amyloid accumulation.
  • This longitudinal study aimed to determine if a combination of specific plasma biomarkers could predict the onset of Aβ pathology in cognitively unimpaired individuals with low baseline brain Aβ levels.
  • Results from multiple cohorts revealed that combining plasma %p-tau217 and Aβ42/40 levels significantly improved the detection of abnormal Aβ status, indicating a promising strategy for early intervention in Alzheimer's disease.
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  • Researchers aimed to evaluate a blood test for Alzheimer’s disease (AD) to simplify diagnosis and treatment in both primary and secondary care settings.* -
  • The study involved 1213 patients with cognitive symptoms, measuring specific biomarkers in their plasma to determine the presence of AD pathology.* -
  • Results showed that about 50% of the patients had AD pathology, with data collected indicating significant diagnostic accuracy and potential for practical application.*
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Introduction: Cerebrospinal fluid (CSF) tau phosphorylation at multiple sites is associated with cortical amyloid and other pathologic changes in Alzheimer's disease. These relationships can be non-linear. We used an artificial neural network to assess the ability of 10 different CSF tau phosphorylation sites to predict continuous amyloid positron emission tomography (PET) values.

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Background: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relation between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans.

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Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests.

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Article Synopsis
  • The Knight-Alzheimer Disease Research Center at Washington University has been at the forefront of Alzheimer disease research for over 40 years, significantly enhancing our understanding through various studies on cognitive and molecular aspects.
  • Over 26,000 biological samples have been collected from participants, including DNA, RNA, plasma, and cerebrospinal fluid, to support extensive research on dementia and aging.
  • The Genetics and High Throughput -Omics core has conducted in-depth molecular profiling to discover new risk factors, biomarkers, and potential treatment targets for Alzheimer disease.
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  • The study investigated the role of neurodegeneration markers (neurogranin, neurofilament light, and hippocampal volume) in Alzheimer's disease using cerebrospinal fluid proteomics.
  • A small number of individuals exhibited both amyloid and tau pathology with either neurogranin or neurofilament light, showing distinct proteomic profiles based on these markers.
  • The findings suggest that neurogranin might not be the best indicator of neurodegeneration and that different markers provide unique insights into the disease, helping refine staging beyond just amyloid and tau levels.
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  • * A study involving 100 MS patients found that the rate of amyloid-β biomarker positivity was about half compared to 300 non-MS controls, indicating a lower risk of Alzheimer’s in MS patients.
  • * Most MS patients with amyloid-β pathology exhibited atypical symptoms for MS, suggesting that the relationship between MS and Alzheimer’s disease could lead to new research opportunities.
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