1,721,005 research outputs found
18F-FDG-PET in Mouse Models of Alzheimer's Disease
Full text linkSuitable animal models and in vivo biomarkers are essential for development and evaluation of new therapeutic strategies in Alzheimer's disease (AD). 18F-Fluorodeoxyglucose (18F-FDG)-positron-emission tomography (PET) is an imaging biomarker that allows the assessment of cerebral glucose metabolism in vivo. While 18F-FDG-PET/CT is an established tool in the evaluation of AD patients, its role in preclinical studies with AD mouse models remains unclear. Here, we want to review available studies on 18F-FDG-PET/CT in AD mouse models in order to evaluate the method and its impact in preclinical AD research. Only a limited number of studies using 18F-FDG-PET in AD mice were carried out so far showing contradictory findings in cerebral FDG uptake. Methodological differences as well as underlying pathological features of used mouse models seem to be accountable for those varying results. However, 18F-FDG-PET can be a valuable tool in longitudinal in vivo therapy monitoring with a lot of potential for future studies
18F-FDG-PET and Multimodal Biomarker Integration: A Powerful Tool for Alzheimer’s Disease Diagnosis
No full textAbstract An early, biomarker-based diagnosis of Alzheimer’s Disease (AD) is crucial, especially with the emerging availability of novel therapeutic options. However, the role of 18 F-FDG-PET and its relationship to other PET and CSF biomarkers remains unclear. Therefore, the aim of this study was the evaluation of the role of 18 F-FDG-PET in AD diagnosis and its relationship to other commonly used fluid and PET biomarkers and their individual and multimodal accuracy in AD diagnosis. We included n = 157 AD patients, n = 603 MCI patients, and n = 380 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) that underwent PET imaging with 18 F-FDG or 18 F-Florbetapir. Clinical and imaging data including patient characteristics, CSF biomarkers, cognition tests, 18 F-FDG-PET, 18 F-Florbetapir-PET, and 18 F-Flortaucipir-PET were retrospectively analyzed. PET images were quantified in several brain regions. The uptake of 18 F-FDG was inversely correlated with 18 F-Florbetapir and positively correlated with CSF Aβ42 in several brain regions commonly affected by AD. Additionally, 18 F-FDG uptake showed an inverse correlation with both forms of CSF tau, t-tau and p-tau, in various brain regions, but did not correlate with 18 F-Flortaucipir uptake. Moreover, regional 18 F-FDG uptake was positively correlated with cognitive function. Diagnostic accuracies were similarly high for 18 F-FDG uptake in the PCC/Precuneus region, 18 F-Florbetapir uptake, CSF Aβ42, CSF p-tau, and 18 F-Flortaucipir uptake in differentiating AD from cognitively normal individuals. 18 F-FDG-PET and its combination with CSF p-tau/ Aβ42 ratio showed the highest predictive power for disease severity. The study underscores the potential of integrating 18 F-FDG-PET with CSF biomarkers to enhance the diagnosis, prognosis, and monitoring of AD, highlighting the complexity and regional specificity of biomarker interactions in neurodegeneration
Neuron Loss and Behavioral Deficits in the TBA42 Mouse Model Expressing N-Truncated Pyroglutamate Amyloid-β3–42
No full textPyroglutamate-modified amyloid-beta (A beta) at amino acid position three (A beta(pE3-42)) is gaining considerable attention as a potential key player in the pathogenesis of Alzheimer's disease (AD). A beta(pE3-42) is abundant in AD brain and has a high aggregation propensity, stability, and cellular toxicity. The aim of the present work was to study the effect of A beta(pE3-42) expression on neuron loss and associated behavioral deficits using the TBA42 transgenic mouse model. Expression of pyroglutamate A beta(3-42) triggers hippocampal CA1 neuron loss and behavioral deficits in the TBA42 mouse model. Mice elicited significant neuron death (-35% at the age of 12 months), deficits in the spatial reference memory, working memory, loss of anxiety, and severe motor deficits in an age-dependent manner. These results support a major pathological function of pyroglutamate A beta in AD
Synaptic Alterations in Mouse Models for Alzheimer Disease—A Special Focus on N-Truncated Abeta 4-42
No full textThis commentary reviews the role of the Alzheimer amyloid peptide Aβ on basal synaptic transmission, synaptic short-term plasticity, as well as short- and long-term potentiation in transgenic mice, with a special focus on N-terminal truncated Aβ4-42. Aβ4-42 is highly abundant in the brain of Alzheimer’s disease (AD) patients. It demonstrates increased neurotoxicity compared to full length Aβ, suggesting an important role in the pathogenesis of AD. Transgenic Tg4-42 mice, a model for sporadic AD, express human Aβ4-42 in Cornu Ammonis (CA1) neurons, and develop age-dependent hippocampal neuron loss and neurological deficits. In contrast to other transgenic AD mouse models, the Tg4-42 model exhibits synaptic hyperexcitability, altered synaptic short-term plasticity with no alterations in short- and long-term potentiation. The outcomes of this study are discussed in comparison with controversial results from other AD mouse models
In vivo Imaging With 18F-FDG- and 18F-Florbetaben-PET/MRI Detects Pathological Changes in the Brain of the Commonly Used 5XFAD Mouse Model of Alzheimer's Disease
No full textImaging biomarkers of Alzheimer's disease (AD) that are able to detect molecular changes in vivo and transgenic animal models mimicking AD pathologies are essential for the evaluation of new therapeutic strategies. Positron-emission tomography (PET) using either 18F-Fluorodeoxyglucose (18F-FDG) or amyloid-tracers is a well-established, non-invasive tool in the clinical diagnostics of AD assessing two major pathological hallmarks. 18F-FDG-PET is able to detect early changes in cerebral glucose metabolism and amyloid-PET shows cerebral amyloid load. However, the suitability of 18F-FDG- and amyloid-PET in the widely used 5XFAD mouse model of AD is unclear as only a few studies on the use of PET biomarkers are available showing some conflicting results. The aim of this study was the evaluation of 18F-FDG-PET and amyloid-PET in 5XFAD mice in comparison to neurological deficits and neuropathological changes. Seven- and 12-month-old male 5XFAD mice showed a significant reduction in brain glucose metabolism in 18F-FDG-PET and amyloid-PET with 18F-Florbetaben demonstrated an increased cerebral amyloid deposition (n = 4–6 per group). Deficits in spatial reference memory were detected in 12-month-old 5XFAD mice in the Morris Water Maze (n = 10–12 per group). Furthermore, an increased plaque load and gliosis could be proven immunohistochemically in 5XFAD mice (n = 4–6 per group). PET biomarkers 18F-FDG and 18F-Florbetaben detected cerebral hypometabolism and increased plaque load even before the onset of severe memory deficits. Therefore, the 5XFAD mouse model of AD is well-suited for in vivo monitoring of AD pathologies and longitudinal testing of new therapeutic approaches.Open-Access-Publikationsfonds 202
Effects of a citalopram treatment on the amyloid-β-pathology and behaviour in the 5xFAD Alzheimer mouse model
No full textmiRNA Alterations Elicit Pathways Involved in Memory Decline and Synaptic Function in the Hippocampus of Aged Tg4-42 Mice
Full text linkThe transcriptome of non-coding RNA (ncRNA) species is increasingly focused in Alzheimer’s disease (AD) research. NcRNAs comprise, among others, transfer RNAs, long non-coding RNAs and microRNAs (miRs), each with their own specific biological function. We used smallRNASeq to assess miR expression in the hippocampus of young (3 month old) and aged (8 month old) Tg4-42 mice, a model system for sporadic AD, as well as age-matched wildtype controls. Tg4-42 mice express N-truncated Aβ4–42, develop age-related neuron loss, reduced neurogenesis and behavioral deficits. Our results do not only confirm known miR-AD associations in Tg4-42 mice, but more importantly pinpoint 22 additional miRs associated to the disease. Twenty-five miRs were differentially expressed in both aged Tg4-42 and aged wildtype mice while eight miRs were differentially expressed only in aged wildtype mice, and 33 only in aged Tg4-42 mice. No significant alteration in the miRNome was detected in young mice, which indicates that the changes observed in aged mice are down-stream effects of Aβ-induced pathology in the Tg4-42 mouse model for AD. Targets of those miRs were predicted using miRWalk. For miRs that were differentially expressed only in the Tg4-42 model, 128 targets could be identified, whereas 18 genes were targeted by miRs only differentially expressed in wildtype mice and 85 genes were targeted by miRs differentially expressed in both mouse models. Genes targeted by differentially expressed miRs in the Tg4-42 model were enriched for negative regulation of long-term synaptic potentiation, learning or memory, regulation of trans-synaptic signaling and modulation of chemical synaptic transmission obtained. This untargeted miR sequencing approach supports previous reports on the Tg4-42 mice as a valuable model for AD. Furthermore, it revealed miRs involved in AD, which can serve as biomarkers or therapeutic targets
Donanemab detects a minor fraction of amyloid-β plaques in post-mortem brain tissue of patients with Alzheimer’s disease and Down syndrome
No full textGeorg-August-Universität Göttinge
The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice
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