97 research outputs found
Cerebral rituximab uptake in multiple sclerosis: A (89)Zr-immunoPET pilot study
Previous studies have demonstrated that the chimeric monoclonal antibody rituximab significantly reduces clinical and radiological disease activity in relapsing-remitting multiple sclerosis as early as 4βweeks after the first administration. The exact mechanisms leading to this rapid effect have not yet been clarified. The aim of this positron emission tomography study was to assess central nervous system penetration as a possible explanation, using zirconium-89-labelled rituximab. No evidence was found for cerebral penetration of [(89)Zr]rituximab
Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort: The ABIDE project
Introduction
The objective of this study was to assess the usefulness of the appropriate use criteria (AUC) for amyloid imaging in an unselected cohort.
Methods
We calculated sensitivity and specificity of appropriate use (increased confidence and management change), as defined by Amyloid Imaging Taskforce in the AUC, and other clinical utility outcomes. Furthermore, we compared differences in postβpositron emission tomography diagnosis and management change between βAUC-consistentβ and βAUC-inconsistentβ patients.
Results
Almost half (250/507) of patients were AUC-consistent. In both AUC-consistent and AUC-inconsistent patients, postβpositron emission tomography diagnosis (28%β21%) and management (32%β17%) change was substantial. The Amyloid Imaging Taskforce's definition of appropriate use occurred in 55/507 (13%) patients, detected by the AUC with a sensitivity of 93%, and a specificity of 56%. Diagnostic changes occurred independently of AUC status (sensitivity: 57%, specificity: 53%).
Discussion
The current AUC are not sufficiently able to discriminate between patients who will benefit from amyloid positron emission tomography and those who will not
Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design.
INTRODUCTION: The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI). METHODS: ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. RESULTS: Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations. DISCUSSION: Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results
Retinal thickness as a potential biomarker in patients with amyloid-proven early- and late-onset Alzheimer's disease
Introduction: Retinal thickness measured with optical coherence tomography has been proposed as
a noninvasive biomarker for Alzheimerβs disease (AD). We therefore measured retinal thickness in
well-characterized AD and control participants, considering ophthalmological confounders.
Methods: We included 57 amyloid-proven AD cases and 85 cognitively normal, amyloid-negative
controls. All subjects underwent retinal thickness measurements with spectral domain optical
coherence tomography and an ophthalmological assessment to exclude ocular disease.
Results: Retinal thickness did not discriminate cases from controls, including stratified analyses for
early- versus late-onset AD. We found significant associations between macular thickness and global
cortical atrophy [b 20.358; P 5 .01] and parietal cortical atrophy on magnetic resonance imaging
[b 20.371; P , .01] in AD cases.
Discussion: In this study, representing the largest optical coherence tomography cohort with
amyloid-proven AD cases, we show that retinal thickness does not discriminate AD from controls,
despite evident changes on clinical, neuroimaging, and CSF measures, querying the use of retinal
thickness measurements as an AD biomarke
Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases
Neuroinflammation is a process characterised by drastic changes in microglial morphology and by marked upregulation of the 18-kDa translocator protein (TSPO) on the mitochondria. The continual increase in incidence of neuroinflammation and neurodegenerative diseases poses a major health issue in many countries, requiring more innovative diagnostic and monitoring tools. TSPO expression may constitute a biomarker for brain inflammation that could be monitored by using TSPO tracers as neuroimaging agents. From medical imaging perspectives, this review focuses on the current concepts related to the TSPO, and discusses briefly on the status of its PET imaging related to neuroinflammation and neurodegenerative diseases in humans
Place preference induced by nucleus accumbens amphetamine is impaired by local blockade of Group II metabotropic glutamate receptors in rats
BACKGROUND: The nucleus accumbens (NAc) plays a critical role in amphetamine-produced conditioned place preference (CPP). In previous studies, NAc basal and amphetamine-produced DA transmission was altered by Group II mGluR agents. We tested whether NAc amphetamine CPP depends on Group II mGluR transmission. RESULTS: NAc injections (0.5 ΞΌl/side) of the Group II mGluR antagonist (2 S)- a-ethylglutamic acid (EGLU: 0.01β0.8 ΞΌg but not 0.001 ΞΌg) impaired CPP. The drug did not block the acute locomotor effect of amphetamine. CONCLUSION: Results suggest that Group II mGluRs may be necessary for the establishment of NAc amphetamine-produced CPP. These receptors may also mediate other forms of reward-related learning dependent on this structure
Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders
Increasing evidence suggests that epigenetic factors have critical roles in gene
regulation in neuropsychiatric disorders and in aging, both of which are
typically associated with a wide range of gene expression abnormalities. Here,
we have used chromatin immunoprecipitation-qPCR to measure levels of acetylated
histone H3 at lysines 9/14 (ac-H3K9K14), two epigenetic marks associated
with transcriptionally active chromatin, at the promoter regions of eight
schizophrenia-related genes in n=82 postmortem prefrontal
cortical samples from normal subjects and those with schizophrenia and bipolar
disorder. We find that promoter-associated ac-H3K9K14 levels are correlated with
gene expression levels, as measured by real-time qPCR for several genes,
including, glutamic acid decarboxylase 1 (GAD1), 5-hydroxytryptamine
receptor 2C (HTR2C), translocase of outer mitochondrial membrane 70
homolog A (TOMM70A) and protein phosphatase 1E (PPM1E).
Ac-H3K9K14 levels of several of the genes tested were significantly negatively
associated with age in normal subjects and those with bipolar disorder, but not
in subjects with schizophrenia, whereby low levels of histone acetylation were
observed in early age and throughout aging. Consistent with this observation,
significant hypoacetylation of H3K9K14 was detected in young subjects with
schizophrenia when compared with age-matched controls. Our results demonstrate
that gene expression changes associated with psychiatric disease and aging
result from epigenetic mechanisms involving histone acetylation. We further find
that treatment with a histone deacetylase (HDAC) inhibitor alters the expression
of several candidate genes for schizophrenia in mouse brain. These findings may
have therapeutic implications for the clinical use of HDAC inhibitors in
psychiatric disorders
Using blood cytokine measures to define high inflammatory biotype of schizophrenia and schizoaffective disorder
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