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16 results for “Preclinical Biomarkers”
Establish Diagnostic and Prognostic Models for Preclinical AD Patients Based on Multimodal MRI, Behavioral, Genetic, and Plasma Biomarkers
ClinicalTrials.gov study NCT06561906. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.
Data from: White matter hyperintensities and CSF AD biomarkers in preclinical Alzheimer's disease
Objective: Recent studies suggest that white matter hyperintensities (WMH) on MRI, which primarily reflect small vessel cerebrovascular disease, may play a role in the evolution of Alzheimer's disease (AD). In a longitudinal study, we investigated whether WMH promote the progression of AD pathology, or alter the association between AD pathology and risk of progression from normal cognition to mild cognitive impairment (MCI). Methods: Two sets of analyses were conducted. The relationship between whole brain WMH load, based on FLAIR MRI images, obtained in initially cognitively normal participants (n=274) and time to onset of symptoms of MCI (n=60) was examined using Cox regression models. In a subset of the participants with both MRI and CSF data (n=204), the interaction of WMH load and CSF AD biomarkers was also evaluated. Results: Baseline WMH load interacted with CSF t-tau with respect to symptom onset, but not with CSF abeta1-42 or p-tau181. WMH volume was associated with time to symptom onset of MCI among individuals with low t-tau [HR=1.35, CI=1.06-1.73, p=0.013], but not those with high t-tau [HR=0.86,CI=0.56-1.32, p=0.47]. The rate of change in the CSF biomarkers over time was not associated with the rate of change in WMH volumes. Conclusions and Relevance: These results suggest that WMH primarily affect the risk of progression when CSF measures of neurodegeneration or neuronal injury (as reflected by t-tau) are low. However, CSF biomarkers of amyloid and p-tau and WMH appear to have largely independent and non-synergistic effects on the risk of progression to MCI.
CSF synaptic biomarkers in the preclinical stage of Alzheimer's disease and their association with MRI and PET markers of neurodegeneration: a cross-sectional study
<p>Objective: To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer's <i>continuum</i> and associated with Alzheimer's disease (AD) risk factors, primary pathology, and neurodegeneration markers.</p> <p>Methods: Cross-sectional study in the ALFA+ cohort, comprising middle-aged cognitively unimpaired participants. CSF neurogranin and GAP-43 were measured using immunoassays and SNAP-25 and synaptotagmin-1 using immunoprecipitation mass spectrometry. AD CSF biomarkers Aβ42/40, p-tau and t-tau, and the neurodegeneration biomarker NfL were also measured. Participants underwent structural MRI, and <span>fluorodeoxyglucose and</span> Aβ<span> PET imaging. General linear modeling was used to test the associations between CSF synaptic biomarkers and risk factors, </span>Aβ<span> pathology, tau pathology, and neurodegeneration markers.</span></p> <p>Results: All CSF synaptic biomarkers increased with age. CSF neurogranin was higher in females, while CSF SNAP-25 was higher in <i>APOE-</i>ε4 carriers. All CSF synaptic biomarkers increased with higher Aβ load (as measured by CSF Aβ42/40 and Aβ PET Centiloid values) and, importantly, the synaptic biomarkers were increased even in individuals in the earliest stages of Aβ deposition. Higher CSF synaptic biomarkers were also associated with higher CSF p-tau and NfL. Higher CSF neurogranin and GAP-43 were significantly associated with higher brain metabolism, but lower cortical thickness in AD-related brain regions.</p> <p>Conclusion: CSF synaptic biomarkers increase in early preclinical stages of the Alzheimer's <i>continuum </i>even when a low burden of Aβ pathology is present, and they differ in their association with age, sex, <i>APOE-</i>ε4<i>,</i> and markers of neurodegeneration.</p>
Association of CSF biomarkers with hippocampal-dependent memory in preclinical Alzheimer disease
<p><b>Objective: </b>To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer's disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Ab<sub>42</sub>/Ab<sub>40 </sub>and p-tau<sub>181</sub> in cognitively unimpaired older adults (CU).</p> <p><b>Methods: </b>CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Ab<sub>42</sub>,<sub> </sub>Ab<sub>40</sub>, and phosopho-tau<sub>181</sub> (p-tau<sub>181</sub>) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied 'target' objects, novel 'foil' objects, and perceptually similar 'lure' objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.</p> <p><span><b>Results: </b>Age and lower Ab<sub>42</sub>/Ab<sub>40 </sub>were independently associated with elevated p-tau<sub>181</sub>. Age, Ab<sub>42</sub>/Ab<sub>40,</sub> and p-tau<sub>181</sub> were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Ab<sub>42</sub>/Ab<sub>40 </sub>on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Ab<sub>42 </sub>was not significantly associated with p-tau<sub>181 </sub>or memory. </span></p> <p><b>Conclusions: </b>Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.<b> </b></p>
Data from: White matter hyperintensities and CSF AD biomarkers in preclinical Alzheimer’s disease
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Association of CSF biomarkers with hippocampal-dependent memory in preclinical Alzheimer disease
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CSF synaptic biomarkers in the preclinical stage of Alzheimer’s disease and their association with MRI and PET markers of neurodegeneration: a cross-sectional study
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Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement Preclinically and Improves Cardiovascular Health Biomarkers in Humans [mouse_cardiac_aging]
GEO Series GSE283273. Mus musculus. 18 samples. Type: Expression profiling by high throughput sequencing.
Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement Preclinically and Improves Cardiovascular Health Biomarkers in Humans
GEO Series GSE283003. Rattus norvegicus. 12 samples. Type: Expression profiling by high throughput sequencing.
Interferon-stimulated neutrophils identified in preclinical models may serve as a potential biomarker for immunotherapy response in human
GEO Series GSE226962. Mus musculus. 2 samples. Type: Expression profiling by high throughput sequencing.
Multi-modal proteomic target discovery and orthogonol confirmation of preclinical diabetic retinopathy drug development biomarkers
GEO Series GSE20886. Rattus norvegicus. 9 samples. Type: Expression profiling by array.
Discover preclinical biomarkers of hepatotoxicity: Acetaminophen and Carbon tetrachloride
GEO Series GSE32891. Rattus norvegicus. 96 samples. Type: Expression profiling by array.
Cognitive Detection of Preclinical AD: Validation Using Biomarkers
ClinicalTrials.gov study NCT02616679. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Imaging Biomarkers in Preclinical and Symptomatic AD
ClinicalTrials.gov study NCT04134923. IPD Sharing: NO. Countries: 1. Publications: 0.
Preclinical Imaging Biomarkers of Alzheimer's Disease Neuropathology in Young Adults With Youth-onset Diabetes: a Proof-of-concept Study
ClinicalTrials.gov study NCT05350514. IPD Sharing: NO. Countries: 1. Publications: 0.
Skeletal-Muscle Glutamate-Ammonia Ligase as Potential Biomarker of Preclinical Prion Diseases
GEO Series GSE210128. Mus musculus. 173 samples. Type: Expression profiling by high throughput sequencing.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.