ArticleAlzheimer's & dementia (New York, N. Y.)2022
Pharmacokinetic, pharmacodynamic, and transcriptomic analysis of chronic levetiracetam treatment in 5XFAD mice: A MODEL-AD preclinical testing core study.
Article in Alzheimer's & dementia (New York, N. Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Levetiracetam restores GABAergic function and network homeostasis following Vps35 deficiency in excitatory neurons.Translational neurodegeneration · 2026Article
- Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Evaluating the Efficacy of Levetiracetam on Non-Cognitive Symptoms and Pathology in a Tau Mouse Model.Biomedicines · 2024Article
- An exploratory computational analysis in mice brain networks of widespread epileptic seizure onset locations along with potential strategies for effective intervention and propagation control.Frontiers in computational neuroscience · 2024Article
- Network analysis identifies strain-dependent response to tau and tau seeding-associated genes.The Journal of experimental medicine · 2023Article
- Alzheimer risk-increasing TREM2 variant causes aberrant cortical synapse density and promotes network hyperexcitability in mouse models.Neurobiology of disease · 2023Article
- Cortical cerebrovascular and metabolic perturbations in the 5xFAD mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Levetiracetam modulates brain metabolic networks and transcriptomic signatures in the 5XFAD mouse model of Alzheimer's disease.Frontiers in neuroscience · 2023Article
- Pharmacokinetic, pharmacodynamic, and transcriptomic analysis of chronic levetiracetam treatment in 5XFAD mice: A MODEL-AD preclinical testing core study.Alzheimer's & dementia (New York, N. Y.) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
Introduction: Hyperexcitability and epileptiform activity are commonplace in Alzheimer's disease (AD) patients and associated with impaired cognitive function. The anti-seizure drug levetiracetam (LEV) is currently being evaluated in clinical trials for ability to reduce epileptiform activity and improve cognitive function in AD. The purpose of our studies was to establish a pharmacokinetic/pharmacodynamic (PK/PD) relationship with LEV in an amyloidogenic mouse model of AD to enable predictive preclinical to clinical translation, using the rigorous preclinical testing pipeline of the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease Preclinical Testing Core. Methods: A multi-tier approach was applied that included quality assurance and quality control of the active pharmaceutical ingredient, PK/PD modeling, positron emission tomography/magnetic resonance imaging (PET/MRI), functional outcomes, and transcriptomics. 5XFAD mice were treated chronically with LEV for 3 months at doses in line with those allometrically scaled to the clinical dose range. Results: Pharmacokinetics of LEV demonstrated sex differences in Cmax, AUC Discussion: This study represents the first report of PK/PD assessment of LEV in 5XFAD mice. Overall, these results highlighted non-linear kinetics based on dose and sex. Plasma concentrations of the 10 mg/kg dose in 5XFAD overlapped with human plasma concentrations used for studies of mild cognitive impairment, while the 30 and 56 mg/kg doses were reflective of doses used to treat seizure activity. Post-treatment gene expression analysis demonstrated LEV dose-related changes in immune function and neuronal-signaling pathways relevant to human AD, and aligned with regional Highlights: Significant sex differences in pharmacokinetics of levetiracetam were observed in 5XFAD mice.Plasma concentrations of 10 mg/kg levetiracetam dose in 5XFAD overlapped with human plasma concentration used in the clinic.Drug- and dose-related differences in gene expression relevant to human brain regions and pathways were also similar to brain region-specific changes in 18F-fluorodeoxyglucose uptake.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.